Imidazole, triazole and tetrazole derivatives

ABSTRACT

A class of substituted imidazole, triazole and tetrazole derivatives are selective agonists of 5-HT 1  -like receptors and are therefore useful in the treatment of clinical conditions, in particular migraine and associated disorders, for which a selective agonist of these receptors is indicated.

This is a division of application Ser. No. 08/156,140 filed Nov. 22,1993, U.S. Pat. No. 5,451,588, which is a division of Ser. No.07/827,187 filed Jan. 28, 1992, U.S. Pat. No. 5,298,520.

The present invention relates to a class of substituted imidazole,triazole and tetrazole derivatives which act on 5-hydroxytryptamine(5-HT) receptors, being selective agonists of so-called "5-HT₁ -like"receptors. They are therefore useful in the treatment of clinicalconditions for which a selective agonist of these receptors isindicated.

5-HT₁ -like receptor agonists which exhibit selective vasoconstrictoractivity have recently been described as being of use in the treatmentof migraine (see, for example, A. Doenicks et al., The Lancet, 1988,Vol. 1, 1309-11). The compounds of the present invention, beingselective 5-HT₁ -like receptor agonists, are accordingly of particularuse in the treatment of migraine and associated conditions, e.g. clusterheadache, chronic paroxysmal hemicrania, headache associated withvascular disorders, tension headache and paediatric migraine.

EP-A-0313397 describes a class of tryptamine derivatives substituted bya five-membered heteroaliphatic ring, which are stated to be specific toa particular type of "5-HT₁ -like" receptor and thus to be effectivetherapeutic agents for the treatment of clinical conditions,particularly migraine, requiring this activity. However, EP-A-0313397neither discloses nor suggests the imidazole, triazole and tetrazolederivatives provided by the present invention.

The present invention provides a compound of formula I, or a salt orprodrug thereof: ##STR1## wherein the broken circle represents twonon-adjacent double bonds in any position in the five-membered ring;

two, three or four of V, W, X, Y and Z represent nitrogen and theremainder represent carbon provided that, when two of V, W, X, Y and Zrepresent nitrogen and the remainder represent carbon, then the saidnitrogen atoms are in non-adjacent positions within the five-memberedring;

A¹ represents hydrogen, hydrocarbon, a heterocyclic group, halogen,cyano, trifluoromethyl, --OR^(x), --SR^(x), --NR^(x) R^(y), --NR^(x)COR^(y), --NR^(x) CO₂ R^(y), --NR^(x) SO₂ R^(y), or --NR^(z) CTNR^(x)R^(y) ;

A² represents a non-bonded electron pair when four of V, W, X, Y and Zrepresent nitrogen and the other represents carbon; or, when two orthree of V, W, X, Y and Z represent nitrogen and the remainder representcarbon, A² represents hydrogen, hydrocarbon, a heterocyclic group,halogen, cyano, trifluoromethyl, --OR^(x), --SR^(x), --NR^(x) R^(y),--NR^(x) COR^(y), --NR^(x) CO₂ R^(y), --NR^(x) SO₂ R^(y), or --NR_(z)CTNR^(x) R^(y) ;

E represents a bond or a straight or branched alkylene chain containingfrom 1 to 4 carbon atoms;

F represents a group of formula ##STR2## U represents nitrogen or C--R²; B represents oxygen, sulphur or N--R³ ;

R¹ represents --CH₂.CHR⁴ NR⁶ R⁷ or a group of formula ##STR3## in whichthe broken line represents an optional chemical bond; R², R³, R⁴, R⁵, R⁶and R⁷ independently represent hydrogen or C₁₋₆ alkyl;

R^(x) and R^(y) independently represent hydrogen, hydrocarbon or aheterocyclic group, or R^(x) and R^(y) together represent a C₂₋₆alkylene group;

R^(z) represents hydrogen, hydrocarbon or a heterocyclic group;

T represents oxygen, sulphur or a group of formula ═N.G; and

G represents hydrocarbon, a heterocyclic group or anelectron-withdrawing group.

The present invention also provides compounds of formula I above whereinthree or four of V, W, X, Y and Z represent nitrogen and the remainderrepresent carbon;

A² represents a non-bonded electron pair when four of V, W, X, Y and Zrepresent nitrogen and the other represents carbon; or, when three of V,W, X, Y and Z represent nitrogen and the remainder represent carbon, A²represents hydrogen, hydrocarbon, a heterocyclic group, halogen, cyano,trifluoromethyl, --OR^(x), --SR^(x), --NR^(x) R^(y), --NR^(x) COR^(y),--NR^(x) CO₂ R^(y), --NR^(x) SO₂ R^(y), or --NR^(z) CTNR^(x) R^(y) ; and

A¹, E, F, R^(x), R^(y), R^(z) and T are as defined above.

For use in medicine, the salts of the compounds of formula I will benon-toxic pharmaceutically acceptable salts. Other salts may, however,be useful in the preparation of the compounds according to the inventionor of their non-toxic pharmaceutically acceptable salts. Suitablepharmaceutically acceptable salts of the compounds of this inventioninclude acid addition salts which may, for example, be formed by mixinga solution of the compound according to the invention with a solution ofa pharmaceutically acceptable non-toxic acid such as hydrochloric acid,fumaric acid, maleic acid, succinic acid, acetic acid, benzoic acid,oxalic acid, citric acid, tartaric acid, carbonic acid or phosphoricacid. Furthermore, where the compounds of the invention carry an acidicmoiety, suitable pharmaceutically acceptable salts thereof may includealkali metal salts, e.g. sodium or potassium salts; alkaline earth metalsalts, e.g. calcium or magnesium salts; and salts formed with suitableorganic ligands, e.g. quaternary ammonium salts.

The term "hydrocarbon" as used herein includes straight-chained,branched and cyclic groups containing up to 18 carbon atoms, suitably upto 15 carbon atoms, and conveniently up to 12 carbon atoms. Suitablehydrocarbon groups include C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₃₋₇cycloalkyl, C₃₋₇ cycloalkyl(C₁₋₆)alkyl, aryl and aryl(C₁₋₆)alkyl.

The expression "a heterocyclic group" as used herein includes cyclicgroups containing up to 18 carbon atoms and at least one heteroatompreferably selected from oxygen, nitrogen and sulphur. The heterocyclicgroup suitably contains up to 15 carbon atoms and conveniently up to 12carbon atoms, and is preferably linked through carbon. Examples ofsuitable heterocyclic groups include C₃₋₇ heterocycloalkyl,heterocycloalkyl(C₁₋₆)alkyl, heteroaryl and heteroaryl(C₁₋₆)alkylgroups.

Suitable alkyl groups include straight-chained and branched alkyl groupscontaining from 1 to 6 carbon atoms. Typical examples include methyl andethyl groups, and straight-chained or branched propyl and butyl groups.Particular alkyl groups are methyl, ethyl and t-butyl.

Suitable alkenyl groups include straight-chained and branched alkenylgroups containing from 2 to 6 carbon atoms. Typical examples includevinyl and allyl groups.

Suitable alkynyl groups include straight-chained and branched alkynylgroups containing from 2 to 6 carbon atoms. Typical examples includeethynyl and propargyl groups.

Suitable cycloalkyl groups include groups containing from 3 to 7 carbonatoms. Particular cycloalkyl groups are cyclopropyl and cyclohexyl.

A particular aryl group is phenyl.

Particular aryl(C₁₋₆)alkyl groups include benzyl, phenethyl andphenylpropyl.

Suitable heterocycloalkyl groups include azetidinyl, pyrrolidyl,piperidyl, piperazinyl and morpholinyl groups.

Suitable heteroaryl groups include pyridyl, quinolyl, isoquinolyl,pyridazinyl, pyrimidinyl, pyrazinyl, pyranyl, furyl, benzofuryl,dibenzofuryl, thienyl, benzthienyl, imidazolyl, oxadiazolyl andthiadiazolyl groups.

Particular heteroaryl(C₁₋₆)alkyl groups include pyridylmethyl andpyrazinylmethyl,

The hydrocarbon and heterocyclic groups may in turn be optionallysubstituted by one or more groups selected from C₁₋₆ alkyl, adamantyl,phenyl, halogen, C₁₋₆ haloalkyl, C₁₋₆ aminoalkyl, trifluoromethyl,hydroxy, C₁₋₆ alkoxy, aryloxy, keto, C₁₋₃ alkylenedioxy, nitro, cyano,carboxy, C₂₋₆ alkoxycarbonyl, C₂₋₆ alkoxycarbonyl(C₁₋₆)alkyl, C₂₋₆alkylcarbonyloxy, arylcarbonyloxy, C₂₋₆ alkylcarbonyl, arylcarbonyl,C₁₋₆ alkylthio, C₁₋₆ alkylsulphinyl, C₁₋₆ alkylsulphonyl, arylsulphonyl,NR^(v) R^(w), --NR^(v) COR^(w), --NR^(v) CO₂ R^(w), --NR^(v) SO_(R)^(w), --CH₂ NR^(v) SO₂ R^(w), --NHCONR^(v) R^(w), --CONR^(v) R^(w),--SO₂ NR^(v) R^(w) and --CH₂ SO₂ NR^(v) R^(w), in which R^(v) and R^(w)independently represent hydrogen, C₁₋₆ alkyl, aryl or aryl(C₁₋₆)alkyl,or R^(v) and R^(w) together represent a C₂₋₆ alkylene group.

When R^(x) and R^(y), or R^(v) and R^(w), together represent a C₂₋₆alkylene group, this group may be an ethylene, propylene, butylene,pentamethylene or hexamethylene group, preferably butylene orpentamethylene.

When the group G represents an electron-withdrawing group, this group issuitably cyano, nitro, --COR^(x), --CO₂ R^(x) or --SO₂ R^(x), in whichR^(x) is as defined above.

The term "halogen" as used herein includes fluorine, chlorine, bromineand iodine, especially fluorine.

The present invention includes within its scope prodrugs of thecompounds of formula I above. In general, such prodrugs will befunctional derivatives of the compounds of formula I which are readilyconvertible in vivo into the required compound of formula I.Conventional procedures for the selection and preparation of suitableprodrug derivatives are described, for example, in "Design of Prodrugs"ed. H. Bundgaard, Elsevier, 1985.

Where the compounds according to the invention have at least oneasymmetric centre, they may accordingly exist as enantiomers. Where thecompounds according to the invention possess two or more asymmetriccentres, they may additionally exist as diastereoisomers. It is to beunderstood that all such isomers and mixtures thereof are encompassedwithin the scope of the present invention.

It will be appreciated that the imidazole, triazole and tetrazole ringsof formula I can exist in a variety of canonical forms. These maysuitably be represented by formulae IA to IT as follows: ##STR4##wherein A¹, A², E and F are as defined above. Preferred imidazole,triazole and tetrazole rings of formula I include the rings representedby formulae IA, IC, IG, IH, IL, IM, IN, IP and IQ above, especially IH.

The alkylene chain E may be, for example, methylene, ethylene,1-methylethylene, propylene or 2-methylpropylene. Alternatively, thegroup E may represent a single bond such that the group F in formula Iis attached directly to the five-membered heteroaromatic ring.

The group F is suitably an indole, benzofuran or benzthiophene moiety offormula FA, or an indazole moiety of formula FB: ##STR5## wherein B, R¹,R² and R³ are as defined above. Preferably, the group F represents anindole moiety of structure FC: ##STR6## wherein R¹ R² and R³ are asdefined above, in particular wherein R² and R³ are both hydrogen.

It will be appreciated that when four of V, W, X, Y and Z representnitrogen and the other represents carbon, i.e. when the ring of formulaI is a tetrazole ring, then the group A² will be a non-bonded electronpair. Otherwise, A¹ and A² will independently represent hydrogen,hydrocarbon, a heterocyclic group, halogen, cyano, trifluoromethyl,--OR^(x), --SR^(x), --NR^(x) R^(y), --NR^(x) COR^(y), --NR^(x) CO₂R^(y), --NR^(x) SO₂ R^(y), or --NR^(z) CTNR^(x) R^(y).

Suitable values for the groups A¹ and/or A² include C₁₋₆ alkyl, C₃₋₇cycloalkyl, aryl, aryl(C₁₋₆)alkyl, C₃₋₇ heterocycloalkyl, heteroaryl orheteroaryl(C₁₋₆)alkyl, any of which groups may be optionallysubstituted; and hydrogen, halogen, cyano, trifluoromethyl, C₁₋₆ alkoxy,C₁₋₆ alkylthio or --NR^(x) R^(y), in which R^(x) and R^(y) are asdefined above. Examples of optional substituents on the groups A¹ and/orA² suitably include trifluoromethyl, C₁₋₆ alkoxy, C₂₋₆ alkoxycarbonyl,C₂₋₆ alkylcarbonyl, C₁₋₆ alkylsulphonyl, arylsulphonyl, amino, mono- ordi(C₁₋₆)alkylamino, C₂₋₆ alkylcarbonylamino, arylcarbonylamino, C₂₋₆alkoxycarbonylamino, C₁₋₆ alkylsulphonylamino, arylsulphonylamino, C₁₋₆alkylsulphonylaminomethyl, aminocarbonylamino, mono- ordi(C₁₋₆)alkylaminocarbonylamino, mono- or diarylaminocarbonylamino,pyrrolidylcarbonylamino, aminocarbonyl, mono- ordi(C₁₋₆)alkylaminocarbonyl, C₁₋₆ alkylaminosulphonyl,aminosulphonylmethyl, and mono- or di(C₁₋₆)alkylaminosulphonylmethyl.

Particular values of A¹ and/or A² include hydrogen, methyl,methoxymethyl, aminomethyl, dimethylaminomethyl, acetylaminomethyl,benzoylaminomethyl, t-butoxycarbonylaminomethyl,methylsulphonylaminomethyl, phenylsulphonylaminomethyl,aminocarbonylmethyl, ethyl, aminoethyl, acetylaminoethyl,benzoylaminoethyl, methoxycarbonylaminoethyl, ethoxycarbonylaminoethyl,t-butoxycarbonylaminoethyl, methylsulphonylaminoethyl,aminocarbonylaminoethyl, methylaminocarbonylaminoethyl,t-butylaminocarbonylaminoethyl, phenylaminocarbonylaminoethyl,pyrrolidylcarbonylaminoethyl, cyclopropyl, phenyl,methylsulphonylaminophenyl, aminocarbonylphenyl,methylaminocarbonylphenyl, methylsulphonylaminomethylphenyl,aminosulphonylmethylphenyl, methylaminosulphonylmethylphenyl,dimethylaminosulphonylmethylphenyl, benzyl, trifluoromethylbenzyl,methoxybenzyl, acetylaminobenzyl, methylsulphonylaminobenzyl,aminocarbonylaminobenzyl, aminocarbonylbenzyl,methylaminocarbonylbenzyl, methylsulphonylbenzyl,methylaminosulphonylbenzyl, pyridylmethyl, methoxypyridylmethyl, amino,methylamino, benzylamino, dimethylamino, t-butoxycarbonylaminoethylaminoand methylsulphonylaminoethylamino.

Preferred values of A¹ and/or A² include hydrogen, methyl, ethyl, benzyland amino.

Representative values of R¹ include aminoethyl, N-methylaminoethyl,N,N-dimethylaminoethyl, 4-piperidyl, 1-methyl-4-piperidyl,3-pyrrolidinyl and 1-methyl-3-pyrrolidinyl.

Preferred values for the groups R² to R⁷ are hydrogen and methyl.

A particular sub-class of compounds according to the invention isrepresented by the compounds of formula IIA, and salts and prodrugsthereof: ##STR7## wherein X¹ represents nitrogen or A¹² -C;

n is zero, 1, 2 or 3;

B¹ represents oxygen, sulphur or N-R¹³ ;

A¹¹ and A¹² independently represent C₁₋₆ alkyl, C₂₋₆ alkenyl, C₁₋₆alkynyl, C₃₋₇ cycloalkyl, aryl, aryl(C₁₋₆)alkyl, C₃₋₇ heterocycloalkyl,heteroaryl or heteroaryl(C₁₋₆)alkyl, any of which groups may beoptionally substituted; or hydrogen, halogen, cyano, trifluoromethyl,C₁₋₆ alkoxy, C₁₋₆ alkylthio or --NR^(x) R^(y) ;

R¹², R¹³, R¹⁴, R¹⁶ and R¹⁷ independently represent hydrogen or C₁₋₆alkyl; and

R^(x) and R^(y) independently represent hydrogen, hydrocarbon or aheterocyclic group, or R^(x) and R^(y) together represent a C₁₋₆alkylene group.

Examples of optional substituents on the groups A¹¹ and A¹² suitablyinclude trifluoromethyl, C₁₋₆ alkoxy, C₂₋₆ alkoxycarbonyl, C₂₋₆alkylcarbonyl, C₁₋₆ alkylsulphonyl, arylsulphonyl, amino, mono- ordi(C₁₋₆)alkylamino, C₂₋₆ alkylcarbonylamino, arylcarbonylamino, C₂₋₆alkoxycarbonylamino, C₁₋₆ alkylsulphonylamino, arylsulphonylamino, C₁₋₆alkylsulphonylaminomethyl, aminocarbonylamino, mono- ordi(C₁₋₆)alkylaminocarbonylamino, mono- or diarylaminocarbonylamino,pyrrolidylcarbonylamino, aminocarbonyl, mono- ordi(C₁₋₆)alkylaminocarbonyl, C₁₋₆ alkylaminosulphonyl,aminosulphonylmethyl, and mono- or di(C₁₋₆)alkylaminosulphonylmethyl.

Particular values of A¹¹ and A¹² with respect to formula IIA includehydrogen, methyl, ethyl, benzyl and amino When X¹ represents A¹² -C thegroup A¹¹ is preferably hydrogen or methyl.

Preferably, R¹², R¹³ and R¹⁴ each represents hydrogen. Preferred valuesof R¹⁶ and R¹⁷ with respect to formula IIA include hydrogen and methyl.

Another sub-class of compounds according to the invention is representedby the compounds of formula IIB, and salts and prodrugs thereof:##STR8## wherein Y¹ represents nitrogen or A²² -C;

n is zero, 1, 2 or 3;

B² represents oxygen, sulphur or NR²³ ;

A²¹ and A²² independently represent C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋ 6alkynyl, C₃₋₇ cycloalkyl, aryl, aryl(C₁₋₆) alkyl, C₃₋₇ heterocycloalkyl,heteroaryl or heteroaryl(C₁₋₆)alkyl, any of which groups may beoptionally substituted; or hydrogen, halogen, cyano, trifluoromethyl,C₁₋₆ alkoxy, C₁₋₆ alkylthio or NR^(x) R^(y) ;

R²², R²³, R²⁴, R²⁶ and R²⁷ independently represent hydrogen or C₁₋₆alkyl; and

R^(x) and R^(y) independently represent hydrogen, hydrocarbon or aheterocyclic group, or R^(x) and R^(y) together represent a C₂₋₆alkylene group.

Examples of optional substituents on the groups A²¹ and A²² correspondto those indicated for the groups A¹¹ and A¹² with respect to formulaIIA above. Particular values of A²¹ and A²² with respect to formula IIBinclude hydrogen, methyl, ethyl and benzyl.

Preferably, R²², R²³ and R²⁴ each represents hydrogen. Preferred valuesof R²⁶ and R²⁷ with respect to formula IIB include hydrogen and methyl.

A further sub-class of compounds according to the invention isrepresented by the compounds of formula IIC, and salts and prodrugsthereof: ##STR9## wherein Y² represents nitrogen or A³² -C;

Z¹ represents nitrogen or CH;

n is zero, 1, 2 or 3;

B³ represents oxygen, sulphur or N--R³³ ;

A³¹ and A³² independently represent C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆alkynyl, C₃₋₇ cycloalkyl, aryl, aryl(C₁₋₆)alkyl, C₃₋₇ heterocycloalkyl,heteroaryl or heteroaryl(C₁₋₆)alkyl, any of which groups may beoptionally substituted; or hydrogen, halogen, cyano, trifluoromethyl,C₁₋₆ alkoxy, C₁₋₆ alkylthio or -NR^(x) R^(y) ;

R³¹ represents --CH₂.CHR³⁴.NR³⁶ R³⁷ or a group of formula ##STR10## R³²,R³³, R³⁴, R³⁵, R³⁶ and R³⁷ independently represent hydrogen or C₁₋₆alkyl; and

R^(x) and R^(y) independently represent hydrogen, hydrocarbon or aheterocyclic group, or R^(x) and R^(y) together represent a C₂₋₆alkylene group.

Examples of optional substituents on the groups A³¹ and A³² correspondto those indicated for the groups A¹¹ and A¹² with respect to formulaIIA above. Particular values of A³¹ and A³² with respect to formula IICinclude hydrogen, methyl and amino.

Preferably, R³², R³³ and R³⁴ each represents hydrogen. Preferred valuesof R³⁵, R³⁶ and R³⁷ include hydrogen and methyl.

A still further sub-class of compounds according to the invention isrepresented by the compounds of formula IID, and salts and prodrugsthereof: ##STR11## wherein W¹ represents nitrogen or C-A⁴² ;

n is zero, 1, 2 or 3;

B⁴ represents oxygen, sulphur or N--R⁴³ ;

A⁴¹ and A⁴² independently represent C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆alkynyl, C₃₋₇ cycloalkyl, aryl, aryl(C₁₋₆)alkyl, C₃₋₇ heterocycloalkyl,heteroaryl or heteroaryl(C₁₋₆)alkyl, any of which groups may beoptionally substituted; or hydrogen, halogen, cyano, trifluoromethyl,C₁₋₆ alkoxy, C₁₋₆ alkylthio or --NR^(x) R^(y) ;

R⁴¹ represents --CH₂.CHR⁴⁴.NR⁴⁶ R⁴⁷ or a group of formula ##STR12## R⁴²,R⁴³, R⁴⁴, R⁴⁵, R⁴⁶ and R⁴⁷ independently represent hydrogen or C₁₋₆alkyl; and

R^(x) and R^(y) independently represent hydrogen, hydrocarbon or aheterocyclic group, or R^(x) and R^(y) together represent a C₂₋₆alkylene group.

Examples of optional substituents on the groups A⁴¹ and A⁴² correspondto those indicated for the groups A¹¹ and A¹² with respect to formulaIIA above. Particular values of A⁴¹ and A⁴² with respect to formula IIDinclude hydrogen and methyl.

Preferably, R⁴², R⁴³ and R⁴⁴ each represents hydrogen. Preferred valuesof R⁴⁵, R⁴⁶ and R⁴⁷ include hydrogen and methyl.

Specific compounds within the scope of the present invention include:

2-[5-(2-benzyltetrazol-5-ylmethyl)-1H-indol-3-yl]ethylamine;

2-[5-(1-benzyltetrazol-5-ylmethyl)-1H-indol-3-yl]ethylamine;

N,N-dimethyl-2-[5-(1-methyltetrazol-5-ylmethyl)-1H-indol-3-yl]ethylamine;

N,N-dimethyl-2-[5-(2-methyltetrazol-5-ylmethyl)-1H-indol-3-yl]ethylamine;

N,N-dimethyl-2-[5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl]ethylamine;

N,N-dimethyl-2-[5-(tetrazol-2-ylmethyl)-1H-indol-3-yl]ethylamine;

N,N-dimethyl-2-[5-(tetrazol-1-ylmethyl)-1H-indol-3-yl]ethylamine;

N,N-dimethyl-2-[5-(1-methyl-1,2,4-triazol-5-ylmethyl)-1H-indol-3-yl]ethylamine;

N,N-dimethyl-2-[5-(1-methyl-1,2,4-triazol-3-ylmethyl)-1H-indol-3-yl]ethylamine;

N,N-dimethyl-2-[5-(1,2,3-triazol-1-ylmethyl)-1H-indol-3-yl]ethylamine;

3-(2-aminoethyl)-5-(1-methyltetrazol-5-yl)benzo[b]thiophene;

3-(2-aminoethyl)-5-(2-methyltetrazol-5-yl)benzo[b]thiophene;

3-[2-(N,N-dimethylamino)ethyl]-5-(2-methyltetrazol-5-yl)benzo[b]thiophene;

N,N-dimethyl-2-[5-(2-methylimidazol-1-ylmethyl)-1H-indol-3-yl]ethylamine;

N,N-dimethyl-2-[5-(imidazol-1-ylmethyl)-1H-indol-3-yl]ethylamine;

N,N-dimethyl-2-[5-(2-methylimidazol-1-yl)-1H-indol-3-yl]ethylamine;

N,N-dimethyl-2-[5-(2-ethyltetrazol-5-ylmethyl)-1H-indol-3-yl]ethylamine;

N,N-dimethyl-2-[5-(1-ethyltetrazol-5-ylmethyl)-1H-indol-3-yl]ethylamine;

N,N-dimethyl-2-[5-(1,2,4-triazol-1-yl)-1H-indol-3-yl]ethylamine;

1-methyl-4-[5-(2-methylimidazol-1-yl)-1H-indol-3-yl]piperidine;

1-methyl-4-[5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl]piperidine;

4-[5-(2-methylimidazol-1-yl)-1H-indol-3-yl]piperidine;

4-[5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl]piperidine;

3-[5-(2-methylimidazol-1-yl)-1H-indol-3-yl]pyrrolidine;

1-methyl-3-[5-(2-methylimidazol-1-yl)-1H-indol-3-yl]pyrrolidine;

4-[5-(imidazol-1-yl)-1H-indol-3-yl]piperidine;

4-[5-(1,2,3-triazol-1-yl)-1H-indol-3-yl]piperidine;

1-methyl-4-[5-(imidazol-1-yl)-1H-indol-3-yl]piperidine;

1-methyl-4-[5-(1,2,3-triazol-1-yl)-1H-indol-3-yl]piperidine;

1-methyl-3-[5-(1,2,3-triazol-1-yl)-1H-indol-3-yl]pyrrolidine;

1-methyl-3-[5-(2-methylimidazol-1-ylmethyl)-1H-indol-3-yl]pyrrolidine

1-methyl-3-[5-(imidazol-1-yl)-1H-indol-3-yl]pyrrolidine;

1-methyl-3-[5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl]pyrrolidine;

1-methyl-3-[5-(imidazol-1-ylmethyl)-1H-indol-3-yl]pyrrolidine;

N,N-dimethyl-2-[5-(2-aminoimidazol-1-yl)-1H-indol-3-yl]ethylamine;

N,N-dimethyl-2-[5-(2-aminoimidazol-1-ylmethyl)-1H-indol-3-yl]ethylamine;

N-methyl-2-[5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl]ethylamine;

and salts and prodrugs thereof.

The invention also provides pharmaceutical compositions comprising oneor more compounds of this invention in association with apharmaceutically acceptable carrier. Preferably these compositions arein unit dosage forms such as tablets, pills, capsules, powders,granules, sterile parenteral solutions or suspensions, metered aerosolor liquid sprays, drops, ampoules, auto-injector devices orsuppositories; for oral, parenteral, intranasal, sublingual or rectaladministration, or for administration by inhalation or insufflation. Forpreparing solid compositions such as tablets, the principal activeingredient is mixed with a pharmaceutical carrier, e.g. conventionaltableting ingredients such as corn starch, lactose, sucrose, sorbitol,talc, stearic acid, magnesium stearate, dicalcium phosphate or gums, andother pharmaceutical diluents, e.g. water, to form a solidpreformulation composition containing a homogeneous mixture of acompound of the present invention, or a non-toxic pharmaceuticallyacceptable salt thereof. When referring to these preformulationcompositions as homogeneous, it is meant that the active ingredient isdispersed evenly throughout the composition so that the composition maybe readily subdivided into equally effective unit dosage forms such astablets, pills and capsules. This solid preformulation composition isthen subdivided into unit dosage forms of the type described abovecontaining from 0.1 to about 500 mg of the active ingredient of thepresent invention. The tablets or pills of the novel composition can becoated or otherwise compounded to provide a dosage form affording theadvantage of prolonged action. For example, the tablet or pill cancomprise an inner dosage and an outer dosage component, the latter beingin the form of an envelope over the former. The two components can beseparated by an enteric layer which serves to resist disintegration inthe stomach and permits the inner component to pass intact into theduodenum or to be delayed in release. A variety of materials can be usedfor such enteric layers or coatings, such materials including a numberof polymeric acids and mixtures of polymeric acids with such materialsas shellac, cetyl alcohol and cellulose acetate.

The liquid forms in which the novel compositions of the presentinvention may be incorporated for administration orally or by injectioninclude aqueous solutions, suitably flavoured syrups, aqueous or oilsuspensions, and flavoured emulsions with edible oils such as cottonseedoil, sesame oil, coconut oil or peanut oil, as well as elixirs andsimilar pharmaceutical vehicles. Suitable dispersing or suspendingagents for aqueous suspensions include synthetic and natural gums suchas tragacanth, acacia, alginate, dextran, sodium carboxymethylcellulose,methylcellulose, polyvinylpyrrolidone or gelatin.

In the treatment of migraine, a suitable dosage level is about 0.01 to250 mg/kg per day, preferably about 0.05 to 100 mg/kg per day, andespecially about 0.05 to 5 mg/kg per day. The compounds may beadministered on a regimen of 1 to 4 times per day.

The 1,2,4-triazole compounds of this invention may be prepared by aprocess which comprises reacting a reactive derivative of a carboxylicacid of formula R^(a) --CO₂ H with a compound either of formula III orof formula IV, or a salt thereof: ##STR13## wherein one of R^(a), R^(b)and R^(c) is a group of formula A¹, another is a group of formula A²,and the third is a group of formula -E-F, as defined with reference toformula I above.

Suitable reactive derivatives of the acid R^(a) --CO₂ H include esters,for example C₁₋₄ alkyl esters; thioesters, for examplepyridylthioesters; acid anhydrides, for example (R^(a) --CO)₂ O; acidhalides, for example acid chlorides; orthoesters; and primary, secondaryand tertiary amides.

A preferred reactive derivative of the acid R^(a) --CO₂ H is theiminoether derivative of formula V: ##STR14## where R is C₁₋₄ alkyl.

The reagent of formula III may be generated in situ in the reactionmixture. For example, the reaction may be effected by treating acompound of formula V above with an alkyl hydrazine, e.g. methylhydrazine, followed by a suitable carboxylic acid such as formic acid.

The reaction is conveniently carried out by heating the reagentstogether, optionally in a solvent, for example tetrahydrofuran,dimethylformamide or a lower alkanol such as ethanol, propanol orisopropanol, at about 20° C. to 100° C. for about 1 to 6 hours.

Where R^(a) is a group of formula -E-F and the group F is an indolemoiety of structure FC as defined above, the reactive derivative of acarboxylic acid of formula HO₂ C-E-F may be prepared by reacting acompound of formula VI: ##STR15## wherein Q represents a reactivecarboxylate moiety, and E is as defined above; with a compound offormula VII or a carbonyl-protected form thereof: ##STR16## wherein R²is as defined above and R¹¹ corresponds to the group R¹ as defined aboveor represents a group of formula --CH₂.CHR⁴ D¹, in which R⁴ is asdefined above and D¹ represents a readily displaceable group; followed,where required, by N-alkylation by standard methods to introduce themoiety R³.

Suitable carbonyl-protected forms of the compounds of formula VIIinclude the dimethyl acetal or ketal derivatives.

The readily displaceable group D¹ in the compounds of formula VIIsuitably represents a halogen atom, preferably chlorine. When the moietyR¹¹ in the compounds of formula VII is a group of formula --CH₂.CHR⁴ D¹,the substituent D¹ is displaced in situ under the prevailing reactionconditions to afford a final product of formula I wherein R¹ representsa group of formula --CH₂.CHR⁴.NH₂. The terminal amino group cansubsequently, if desired, be further elaborated using techniques knownfrom the art to give a compound of formula I wherein R¹ represents therequired group of formula --CH₂.CHR⁴.NR⁶ R⁷.

The reaction of compounds VI and VII may be carried out in a single step(Fischer indole synthesis) or by an initial non-cyclising step at alower temperature to give a compound of formula VIII: ##STR17## whereinQ, E, R² and R¹¹ are as defined above; followed by cyclisation using asuitable reagent, such as a polyphosphate ester, to give a compound offormula Q-E-F.

The hydrazines of formula VI may be prepared from the correspondinganilines of formula IX: ##STR18## wherein Q and E are as defined above;by diazotisation followed by reduction. Diazotisation is typicallycarried out using sodium nitrite/conc. HCl and the resulting diazoproduct reduced in situ using, for example, tin(II) chloride/conc. HClor sodium sulphite/conc. HCl.

The anilines of formula IX may be prepared by reduction of thecorresponding nitro compounds of formula X: ##STR19## wherein Q and Eare as defined above; typically by catalytic hydrogenation or usingtin(II) chloride.

Where they are not commercially available, the nitro compounds offormula X may be synthesized by standard methods well known to thoseskilled in the art.

Where R^(a) is a group of formula -E-F and the group F is an indazolemoiety of structure FB as defined above, the reactive derivative of acarboxylic acid of formula HO₂ C-E-F may be prepared by the cyclisationof a compound of formula XI: ##STR20## wherein Q, E and R¹ are asdefined above; and D² represents a readily displaceable group; followed,where required, by N-alkylation by standard methods to introduce themoiety R³.

The cyclisation of compound XI is conveniently achieved in a suitableorganic solvent at an elevated temperature, for example in a mixture ofm-xylene and 2,6-lutidine at a temperature in the region of 140° C.

The readily displaceable group D² in the compounds of formula XIsuitably represents ag C₁₋₄ alkanoyloxy group, preferably acetoxy. WhereD² in the desired compound of formula XI represents acetoxy, thiscompound may be conveniently prepared by treating a carbonyl compound offormula XII: ##STR21## wherein R¹, E and Q are as defined above; or aprotected derivative thereof; with hydroxylamine hydrochloride,advantageously in pyridine at the reflux temperature of the solvent;followed by acetylation with acetic anhydride, advantageously in thepresence of a catalytic quantity of 4-dimethylaminopyridine, indichloromethane at room temperature.

The N-formyl protected derivative of the intermediate of formula XII maybe conveniently prepared by ozonolysis of an indole derivative offormula XIII: ##STR22## wherein R¹, E and Q are as defined above;followed by a reductive work-up, advantageously using dimethylsulphide.

The indole derivative of formula XIII may be prepared by methodsanalogous to those described in the accompanying Examples, or byprocedures well known from the art.

In an alternative process, the triazole compounds according to theinvention may be prepared by a method which comprises reacting acompound of formula XIV: ##STR23## wherein A¹, E and F are as definedabove, Hal represents halogen, and two of V^(a), W^(a), X^(a), Y^(a) andZ^(a), to one of which the group Hal is attached, represent carbon andthe remainder represent nitrogen; with a reagent which provides an anion⁻ A², where A² is as previously defined.

Reagents which may provide the anion ⁻ A² include Grignard reagents A²MgHal (where Hal=halogen); organocuprate reagents such as LiA² ₂ Cu;organolithium reagents A² Li; or compounds which stabilise the anion bymeans of an adjacent activating group such as an ester or enolisableketone function. In this case, the adjacent ester or ketone function maybe retained after the process is complete, or may be removed. Forexample, an ester moiety may be hydrolysed and decarboxylated.

The 1,2,3-triazole compounds according to the present invention may beprepared by a process which comprises the cycloaddition of an alkyne offormula R^(a) --C.tbd.C--R^(b) with an azide of formula R^(c) --N₃,where R^(a), R^(b) and R^(c) are as defined above.

The cycloaddition reaction may be conveniently effected in a suitablesolvent such as tetrahydrofuran, ideally by heating in an autoclave for8 hours.

The tetrazole compounds in accordance with the invention may be preparedby a process which comprises the cycloaddition of a nitrile of formulaN.tbd.C--R^(d) with an azide of formula R^(e) --N₃, where one of R^(d)and R^(e) represents a group of formula A¹ and the other is a group offormula -E-F, as defined previously.

The cycloaddition reaction is conveniently effected by heating thereactants together at an elevated temperature, e.g. a temperature in theregion of 150° C., in a suitable solvent such as N-methylpyrrolid-2-one,advantageously in the presence of triethylamine hydrochloride. Theproduct obtained from the cycloaddition reaction will generally be amixture of isomers substituted by the A¹ group at positions 1 and 2 ofthe tetrazole ring, corresponding to structures IL and IM respectivelyas defined above. These isomers may conveniently be separated usingconventional techniques such as chromatography.

In an alternative process, the tetrazole compounds of the invention maybe prepared by a method which comprises reacting a compound of formulaR^(e) -L with a tetrazole derivative of formula XV: ##STR24## whereinone of R^(d) and R^(e) represents a group of formula A¹ and the other isa group of formula -E-F, as defined above, and L represents a suitableleaving group; in the presence of a base such as triethylamine.

The leaving group L suitably represents halogen, e.g. bromine or iodine,or a sulphonate derivative such as tosylate or mesylate.

The reaction is conveniently carried out in a suitable organic solvent,e.g. acetonitrile, at room temperature.

The tetrazole derivatives of formula XV may be prepared by cycloadditionof a nitrile of formula N.tbd.C--R^(d) with sodium azide, advantageouslyunder the conditions described above for the reaction between thenitrile N.tbd.C--R^(d) and the azide R^(e) --N₃ ; followed byacidification with a mineral acid such as hydrochloric acid.

In a further process, the compounds according to the invention whereinthe group F is an indole moiety of structure FC as defined above may beprepared by a method which comprises reacting a compound of formula##STR25## wherein V, W, X, Y, Z, A¹, A² and E are as defined above; witha compound of formula VII as defined above, or a carbonyl-protected formthereof, e.g. the dimethyl acetal or ketal; followed, where required, byN-alkylation by standard methods to introduce the moiety R³.

As with that between compounds VI and VII, the reaction betweencompounds XVI and VII may be carried out in a single step (Fischerindole synthesis) or by an initial non-cyclising step at a lowertemperature to give a compound of formula XVII: ##STR26## wherein V, W,X, Y, Z, A¹, A², E, R² and R¹¹ are as defined above; followed bycyclisation using a suitable reagent, e.g. a polyphosphate ester.

The hydrazines of formula XVI may be prepared from the correspondinganilines of formula XVIII: ##STR27## wherein V, W, X, Y, Z, A¹, A² and Eare as defined above; by methods analogous to those described above withreference to the compounds of formula IX.

The anilines of formula XVIII may be prepared from the correspondingnitro compounds of formula XIX: ##STR28## wherein V, W, X, Y, Z, A¹, A²and E are as defined above; , by methods analogous to those describedabove with reference to the compounds of formula X.

The nitro compounds of formula XIX may be prepared by a variety ofmethods which will be readily apparent to those skilled in the art. Forexample, where V represents a nitrogen atom, the relevant compounds offormula XIX may be prepared by reacting the anion of a compound offormula XX with a compound of formula XXI: ##STR29## wherein W, X, Y, Z,, A¹, A² and E are as defined above, and represents a readilydisplaceable group.

Where compound XX is a triazole or tetrazole derivative, the anionthereof may be generated by carrying out the reaction in a base such astriethylamine. Where compound XX is an imidazole derivative, the anionthereof may conveniently be generated if the reaction is carried out insodium hydride using N,N-dimethylformamide as solvent. Where salts ofthe compounds of formula XX are commercially available, e.g. the sodiumsalt of 1,2,4-triazole, these are advantageously utilised inN,N-dimethylformamide solution in place of the compounds of formula XXthemselves, with no requirement in this instance for additional base tobe present in the reaction mixture.

The readily displaceable group D³ in the compounds of formula XXI issuitably a halogen atom, preferably bromine; except when the moiety D³is attached directly to the aromatic ring, i.e. when E represents abond, in which case D³³ is preferably fluorine.

Where they are not commercially available, the nitro compounds offormula XXI above may be prepared by procedures analogous to thosedescribed in the accompanying Examples, or by methods well known fromthe art.

In an alternative approach to the 1,2,4-triazole derivatives, the nitrocompounds of formula XIX. may be prepared from those of formula X aboveby appropriate modification of the moiety Q using, for example, methodsanalogous to those described above with reference to the compounds offormulae III and IV. Thus, for example, since Q in the compounds offormula X represents a reactive carboxylate moiety, the compounds offormula XIX may be prepared therefrom by reaction with a compound offormula A² -C(═NNHA¹)NH₂ or A² -C(═NNH₂)NHA¹.

In a still further process, the compounds according to the inventionwherein the group F is an indazole moiety of structure FB as definedabove may be prepared by a method which comprises cyclising a compoundof formula XXII: ##STR30## wherein V, W, X, Y, Z, A¹, A², E, R¹ and D²are as defined above; followed, where required, by N-alkylation bystandard methods to introduce the moiety R³.

As with the cyclisation of compound XI, that of compound XXII isconveniently achieved in a suitable organic solvent at an elevatedtemperature, for example in a mixture of m-xylene and 2,6-lutidine at atemperature in the region of 140° C.

The compounds of formula XXII may, for example, be prepared from thecorresponding compound of formula XXIII: ##STR31## wherein V, W, X, Y,Z, A¹, A², E and R¹ are as defined above; or a protected derivativethereof; which in turn may be prepared from the corresponding compoundof formula XXIV: ##STR32## wherein V, W, X, Y, Z, A¹, A², E and R¹ areas defined above; using methods analogous to those described above withreference to the compounds of formulae XII and XIII. Thus, for example,since Q in the compounds of formula XIII represents a reactivecarboxylate moiety, the 1,2,4-triazole derivatives of formula XXIV maybe prepared therefrom by reaction with a compound of formula A²-C(═NNHA¹)NH² or A² -C(═NNH₂)NHA¹.

In a yet further process, the compounds according to the inventionwherein the group F is a benzofuran or benzthiophene moiety may beprepared by a method which comprises cyclising a compound of formulaXXV: ##STR33## wherein V, W, X, Y, Z, A¹, A², E and R² are as definedabove, B^(a) represents oxygen or sulphur, and R²¹ corresponds tothe-group R¹ as defined above or represents a precursor group thereto asdiscussed below; followed, where required, by conversion of the groupR²¹ into the desired group R¹ by conventional means.

The cyclisation is conveniently effected by using polyphosphoric acid ora polyphosphate ester, advantageously at an elevated temperature.

The compounds of formula XXV may be prepared by reacting a compound offormula XXVI with a compound of formula XXVII: ##STR34## wherein V, W,X, Y, Z, A¹, A², E, B^(a), R² and R²¹ are as defined above, and Halrepesents halogen.

The reaction is conveniently effected in the presence of a base such assodium hydroxide.

The hydroxy and mercapto derivatives of formula XXVI may be prepared bya variety of methods which will be readily apparent to those skilled inthe art. In one such method, the anion of a compound of formula XX asdefined above is reacted with a compound of formula XXVIII: ##STR35##wherein D³, E and B^(a) are as defined above; to afford an intermediateof formula XXVI wherein V is nitrogen.

The compounds of formula XXVII and XXVIII, where they are notcommercially available, may be prepared by standard procedures wellknown in the art.

It will be understood that any compound of formula I initially obtainedfrom any of the above processes may, where appropriate, subsequently beelaborated into a further compound of formula I by techniques known fromthe art. Indeed, as will be appreciated, the compound of formula XVabove in which R^(d) is a group of formula -E-F is itself a compound offormula I in which A¹ is hydrogen and A² represents a non-bondedelectron pair. In particular, a compound of formula I wherein R³ ishydrogen initially obtained may be converted into a compound of formulaI wherein R³ represents C₁₋₆ alkyl, C₂₋₆ alkenyl or C₂₋₆ alkynyl bystandard techniques such as alkylation, for example by treatment with analkyl iodide, e.g. methyl iodide, typically under basic conditions, e.g.sodium hydride in dimethylformamide, or triethylamine in acetonitrile.Similarly, a compound of formula I wherein R¹ represents a group offormula --CH₂.CHR⁴.NH₂ initially obtained may be converted into acompound of formula I wherein R¹ represents a group of formula--CH₂.CHR⁴.NR⁶ R⁷ in which R⁶ and R⁷ are as defined above with theexception of hydrogen, for example by conventional N-alkylation orN-arylation techniques, e.g. by treatment with the appropriate aldehydein the presence of a reducing agent such as sodium cyanoborohydride.

Where the above-described processes for the preparation of the compoundsaccording to the invention give rise to mixtures of stereoisomers, theseisomers may be separated by conventional techniques such as preparativechromatography.

The novel compounds may be prepared in racemic form, or individualenantiomers may be prepared either by enantiospecific synthesis or byresolution. The novel compounds may, for example, be resolved into theircomponent enantiomers by standard techniques, such as the formation ofdiastereomeric pairs by salt formation with an optically active acid,such as (-)-di-p-toluoyl-d-tartaric acid and/or(+)-di-p-toluoyl-1-tartaric acid followed by fractional crystallizationand regeneration of the free base. The novel compounds may also beresolved by formation of diastereomeric esters or amides, followed bychromatographic separation and removal of the chiral auxiliary.

During any of the above synthetic sequences it may be necessary and/ordesirable to protect sensitive or reactive groups on any of themolecules concerned. This may be achieved by means of conventionalprotecting groups, such as those described in Protective Groups inOrganic Chemistry, ed. J. F. W. McOmie, Plenum Press, 1973; and T. W.Greene, Protective Groups in Organic Synthesis, John Wiley & Sons, 1981.The protecting groups may be removed at a convenient subsequent stageusing methods known from the art.

Alternatively, certain of the functional groups on the desired productsmay be carried through the reaction sequence as precursor groups, andthen regenerated from these precursor groups at a late stage in theoverall synthesis. For example, where R¹ in the desired compound offormula I represents a group of formula --(CH₂)₂ NH₂, this group can begenerated from a cyano precursor --CH₂ CN by reduction using, forexample, borane/tetrahydrofuran. The cyano precursor may in turn becarried through the reaction sequence as a methyl group --CH₃, which mayconveniently be converted to --CH₂ CN by treatment withN-bromosuccinimide and benzoyl peroxide, in the presence of a brightlight source, followed by reaction of the resulting bromo intermediatewith sodium cyanide in dimethyl sulphoxide.

The following Examples illustrate the preparation of compounds accordingto the invention.

The ability of test compounds to bind to 5-HT₁ -like receptors wasmeasured in membranes prepared from pig caudate using the proceduredescribed in J. Neurosci., 1987, 7, 894. Binding was determined using 2nM 5-hydroxytryptamine creatinine sulphate, 5-[1,2-³ H(N)] as aradioligand. Cyanopindolol (100 nM) and mesulergine (100 nM) wereincluded in the assay to block out 5-HT_(1A) and 5-HT_(1C) binding sitesrespectively. The concentration of the compounds of the accompanyingExamples required to displace 50% of the specific binding (IC₅₀) isbelow 1 μM in each case.

The activity of test compounds as agonists of the 5-HT₁ -like receptorwas measured in terms of their ability to mediate contraction of thesaphenous vein of New Zealand White rabbits, using the proceduredescribed in Arch. Pharm., 1990, 342, 111. Agonist potencies werecalculated as -log₁₀ EC₅₀ (pECs₅₀) values, from plots of percentage 5-HT(1 μm) response against the concentration of the agonist. The compoundsof the accompanying Examples were found to possess pEC₅₀ values in thisassay of not less than 5.0 in each case.

EXAMPLE 1 2-[5-(2-Benzyltetrazol-5-ylmethyl)-1H-indol-3-yl]ethylamine.Oxalate

1.4-Hydrazinobenzylcyanide. Hydrochloride

A solution of NaNO₂ (80 g, 1.16 mol) was added dropwise to a cooled(-10° C.), stirred, suspension of 4-aminobenzyl cyanide (153.5 g, 1.16mol) in concentrated HCl (1500 ml), at such a rate that the temperaturedid not rise above -10° C. The mixture was stirred at -10° C. for 0.25 hbefore being filtered rapidly under vacuum into an addition funnel. Thesolution was added portionwise over a 0.25 h period to a rapidly stirredmixture of SnCl₂.2H₂ O (1.05 kg, 4.64 mol) in concentrated HCl (800 ml)keeping the temperature below -5° C. The mixture was allowed to warm toroom temperature and stir for 0.25 h before filtering the sandy colouredprecipitate under vacuum and washing with ether (5×500 ml). Theresultant solid was dried over P₂ O₅ in a vacuum oven (80° C.) for 16 hto give the title compound (213 g, 100%), m.p. 181°-183° C.; ¹ H NMR(360 MHz, D₂ O) δ3.90 (2H, s, CH₂); 7.06 (2H, d, J=8.7 Hz, Ar--H); 7.40(2H, d, J=8.7 Hz, Ar--H).

2. 2-(5-Cyanomethyl-1H-indol-3-yl)ethylamine. Hydrochloride

4-Chlorobutanal dimethylacetal (37.07 g, 0.24 mol) was added to astirred solution of 4-hydrazinobenzyl cyanide hydrochloride (47.0 g,0.26 mol) in EtOH/H₂ O (5:1; 21) and refluxed for 4.5 h. The reactionmixture was evaporated to dryness under vacuum, MeOH (150 ml) added, andthe mixture left at 0° C. for 10 h. The resultant pale yellowprecipitate was filtered under vacuum, washed with Et₂ O/MeOH (5:1;2×100 ml) and dried. The product was used without further purification(24.1 g, 40%), m.p. 239°-241° C.; R_(f) 0.4 in CH₂ Cl₂ /EtOH/NH₃(40:8:1); ¹ H NMR (360 MHz, D₂ O) 3.18 (2H, t, J=7.1 Hz, CH₂); 3.36 (2H,t, J=7.1 Hz, CH₂); 4.02 (2H, s, CH₂); 7.22 (1H, dd, J=1.5 and 8.4 Hz,Ar--H); 7.36 (1H, s, Ar--H); 7.56 (1H, d, J=8.4 Hz, Ar--H); 7.66 (1H, s,Ar--H).

3. 2-(5-Tetrazol-5-ylmethyl-1H-indol-3-yl)ethylamine

A solution of 2-(5-cyanomethyl-1H-indol-3-yl)ethylamine hydrochloride(2.5 g, 10.6 mmol), triethylamine hydrochloride (2.2 g, 16.0 mmol) andsodium azide (2.1 g, 32.3 mmol), in 1-methylpyrrolidin-2-one (30 ml) washeated at 140° C. for 8 h. 5N hydrochloric acid (3 ml) was added and thesolvents removed by distillation under vacuum. The residue waschromatographed on silica-gel eluting with EtOH/Et₂ O/H₂ O/NH₃(20:30:8:1) to give the title-tetrazole (1.76 g, 69%); δ (360 MHz, CD₃OD) 3.06 (2H, t, J=7.2 Hz, CH₂); 3.19 (2H, t, J=7.2 Hz, CH₂); 4.29 (2H,s, CH₂); 7.07 (1H, d, J=8.4 Hz, Ar--H); 7.13 (1H, s, Ar--H); 7.29 (1H,d, J=8.4 Hz, Ar--H); 7.44 (1H, s, Ar--H).

4.N-tert-Butyloxycarbonyl-2-(5-tetrazol-5-ylmethyl-1H-indol-3-yl)ethylamine

To a stirred suspension of2-(5-tetrazol-5-ylmethyl-1H-indol-3-yl)ethylamine (1.76 g, 7.27 mmol) indry CH₂ Cl₂ (40 ml) was added triethylamine (1.5 g, 14.9 mmol) and(BOC)₂ O (1.9 g, 7.3 mmol) and the mixture stirred for 16 h. The solventwas removed under vacuum and the residue chromatographed on silica-geleluting with EtOH/Et₂ O/H₂ O/NH₃ (20:60:8:1) to give the title product(1.6 g, 64%); δ (360 MHz, CD₃ OD) 1.41 (9H, s, 3 of CH₃); 2.87 (2H, t,J=7.4 Hz, CH₂); 3.30 (2H, t, J=7.4 Hz, CH₂); 4.32 (2H, s, CH₂); 6.99(1H, d, J=8.3 Hz, Ar--H); 7.04 (1H, s, Ar--H); 7.26 (1H, d, J=8.3 Hz,Ar--H); 7.49 (1H, s, Ar--H).

5.N-tert-Butyloxycarbonyl-2-[5-(2-benzyltetrazol-5-ylmethyl)-1H-indol-3-yl]ethylamineandN-tert-butyloxycarbonyl-2-[5-(1-benzyltetrazol-5-ylmethyl)-1H-indol-3yl]ethylamine

Benzyl bromide (0.31 g, 1.8 mmol) was added to a solution of thetetrazole from step 4 (0.62 g, 1.8 mmol), and triethylamine (0.37 g, 3.6mmol) in dry acetonitrile (20 ml). The mixture was stirred at R.T. for 2h, heated at 70° C. for 1 h and then stirred at R.T. for 16 h. Thesolvent was removed under vacuum and the residue chromatographed throughsilica-gel eluting with CH₂ Cl₂ /MeOH (97:3) to give 2-separated benzyltetrazoles. The less polar isomer was identified as the 2-benzyltetrazole (0.17 g, 22.4%); δ (360 MHz, CDCl₃) 1.43 (9H, s, 3 of CH₃);2.90 (2H, t, J=6.8 Hz, CH₂); 3.41 (2H, br t, CH₂); 4.32 (2H, s, CH₂);5.70 (2H, s, CH₂ Ph); 7.00 (1H, s, Ar--H); 7.15 (1H, d, J=8.4 Hz,Ar--H); 7.28 (1H, d, J=8.4 Hz, Ar--H); 7.34 (5H, s, Ar--H); 7.50 (1H, s,Ar--H); 7.96 (1H, br s, NH).

The more polar component was identified as the 1-benzyltetrazole (0.2 g,26.4%) δ (360 MHz, CDCl₃) 1.43 (9H, s, 3 of CH₃); 2.88 (2H, t, J=7.0 Hz,CH₂); 3.40 (1H, br t, CH₂); 4.26 (2H, s, CH₂); 5.29 (2H, s, CH₂ --Ph);6.92 (1H, d, J=8.4 Hz, Ar--H); 7.01-7.05 (3H, m, Ar--H); 7.27-7.30 (5H,m, Ar--H); 8.08 (1H, br s, NH).

6. 2-[5-(2-Benzyltetrazol-5-ylmethyl)-1H-indol-3-yl]ethylamine. Oxalate

Trifluoroacetic acid (1.5 ml) was added to a solution of the less polarcomponent isolated from step 5 (0.17 g, 0.4 mmol) in CH₂ Cl₂ (5 ml) andstirred at R.T. for 1 h. The solvents were removed under vacuum and theresidue chromatographed through silica-gel eluting with CH₂ Cl₂/EtOH/NH₃ (40:8:1) to give the title-tetrazole. The oxalate salt wasprepared (65 mg); mp 169°-171° C.; (Found: C, 59.23; H, 5.07; N, 19.60.C₁₉ H₂₀ N₆. 1.05 (C₂ H₂ O₄) requires C, 59.36; H, 5.22; N, 19.68%); δ(360 MHz, D₂ O) 3.09 (2H, t, J=6.9 Hz, CH₂); 3.29 (2H, t, J=6.9 Hz,CH₂); 4.30 (2H, s, CH₂); 5.77 (2H, s, CH₂); 7.11 (1H, dd, J=1.6 and 8.4Hz, Ar--H); 7.28 (1H, s, Ar--H); 7.32-7.34 and 7.39-7.41 (5H, m, Ar--H);7.43 (1H, d, J=8.4 Hz, Ar--H); 7.51 (1H, s, Ar--H).

EXAMPLE 2 2-[5-(1-Benzyltetrazol-5-ylmethyl)-1H-indol-3-yl]ethylamine.Hydrochloride. Hemihydrate

Prepared from the more polar component isolated from step 5, Example 1,using the procedure described for step 6, Example 1. The hydrochloridehemihydrate salt was prepared; mp 210°-213° C.; (Found: C, 60.39; H,5.88; N, 22.14. C₁₉ H₂₀ N₆.HCl.₀.5 H₂ O requires C, 60.39; H, 5.87; N,22.24%); δ (250 MHz, D₂ O) 3.02 (2H, t, J=6.8 Hz, CH₂); 3.19 (2H, t,J=6.8 Hz, CH₂); 4.44 (2H, s, CH₂); 5.60 (2H, s, CH₂); 6.95-7.02 (3H, m,Ar--H); 7.16-7.25 (4H, m, Ar--H); 7.28 (1H, s, Ar--H); 7.40 (1H, d,J=8.4 Hz, Ar--H).

EXAMPLE 3N,N-Dimethyl-2-[5-(2-methyltetrazol-5-ylmethyl)-1H-indol-3-yl]ethylamine.Oxalate

1.N-tert-Butyloxycarbonyl-2-[5-(2-methyltetrazol-5-ylmethyl)-1H-indol-3-yl]ethylamineand N-tertbubutyloxycarbonyl-2-[5-(1-methyltetrazol-5-ylmethyl)-1H-indol-3-yl]ethylamine

Methyl iodide (0.44 g, 3.1 mmol) was added to a stirred solution of thetetrazole from step 4, Example 1 (0.95 g, 2.78 mmol) and triethylamine(0.56 g, 5.5 mmol) in dry acetonitrile (15 ml). After 10 h a furtherequivalent of methyl iodide was added and stirred for 16 h. The solventwas removed under vacuum and the residue chromatographed on silica-geleluting with CH₂ Cl₂ /MeOH (97:3) to give the title mixture of 1- and2-methyltetrazoles (0.6 g, 61%); δ (360 MHz, CDCl₃) 1.43 (9H, m, 3 ofCH₃); 2.89-2.92 (2H, m, CH₂); 3.38-3.48 (2H, m, CH₂); 3.83 (2H, s, CH₂);4.28 and 4.40 (total 3H, s, CH₃); 6.98 and 7.17 (total 1H, d, J=8.4 Hz,Ar--H); 7.02 and 7.06 (total 1H, s, Ar--H); 7.30 and 7.31 (total 1H, d,J=8.4 Hz, Ar--H); 7.43 and 7.54 (total 1H, s, Ar--H); 8.00 and 8.10(total 1H, br s, NH).

2. 2-[5-(2-Methyltetrazol-5-ylmethyl)-1H-indol-3-yl]ethylamine and2-[5-(1-methyltetrazol-5-ylmethyl)-1H-indol-3-yl]ethylamine

Prepared from the preceding methyltetrazoles using the proceduredescribed in step 6, Example 1. The crude product was chromatographed onsilica-gel eluting with CH₂ Cl₂ /EtOH/NH₃ (40:8:1) to give 2 separatedcomponents. The less polar product (0.1 g, 24%) was identified as the2-methyltetrazole; δ (360 MHz, CDCl₃) 1.38 (9H, s, 3 of CH₃); 2.88 (2H,t, J=6.6 Hz, CH₂); 3.00 (2H, t, J=6.6 Hz, CH₂); 4.28 (3H, s, CH₃); 4.33(2H, s, CH₂); 7.00 (1H, d, J=8.4 Hz, Ar--H); 7.06 (1H, d, J=2.1 Hz,Ar--H); 7.17 (1H, d, J=8.4 Hz, Ar--H); 7.56 (1H, s, Ar--H); 8.04 (1H, brs, NH).

The more polar product (0.13 g, 31%) was identified as the1-methyltetrazole; δ (360 MHz, CDCl₃) 1.38 (9H, s, 3 of CH₃); 2.86 (2H,t, J=6.6 Hz, CH₂); 3.00 (2H, t, J=6.6 Hz, CH₂); 3.82 (3H, s, CH₃); 4.40(2H, s, CH₂); 6.98 (1H, dd, J=1.6 and 8.3 Hz, Ar--H); 7.06 (1H, d, J=1.6Hz, Ar--H); 7.31 (1H, d, J=8.3 Hz, Ar--H); 7.41 (1H, s, Ar--H); 8.18(1H, br s, NH).

3.N,N-Dimethyl-2-[5-(2-methyltetrazol-5-ylmethyl)-1H-indol-3-yl]ethylamine.Oxalate

A solution of formaldehyde (80 mg of a 30% solution) in methanol (15 ml)was added to a stirred solution of2-[5-(2-methyltetrazol-5-ylmethyl)-1H-indol-3-yl]ethylamine (0.1 g, 0.4mmol), NaCNBH₃ (60 mg) and glacial acetic acid (0.12 g) in methanol (15ml). The solution was stirred for 2 h, basified with K₂ CO₃ solution andthe MeOH removed under vacuum. The crude product obtained afterextraction into ethylacetate and removal of solvent was chromatographedthrough silica-gel eluting with CH₂ Cl₂ /EtOH/NH₃ (40:8:1) to give thedesired N,N-dimethyltryptamine (96 mg, 87%). The oxalate salt wasprepared: mp 185°-187° C. (MeOH/Et₂ O); (Found: C, 54.42; H, 5.74; N,22.53.C₁₅ H₂₀ N₆.C₂ H₂ O₄ requires C, 54.54; H, 5.92; N, 22.45%); δ (360MHz, D₂ O) 2.91 (6H, s, 2 of CH₃); 3.21 (2H, t, J=7.4 Hz, CH₂); 3.47(2H, t, J=7.4 Hz, CH₂); 4.30 (3H, s, CH₃); 4.34 (2H, s, CH₂); 7.17 (1H,dd, J=1.5 and 8.4 Hz, Ar--H); 7.33 (1H, s, Ar--H); 7.48 (1H, d, J=8.4Hz, Ar--H); 7.59 (1H, s, Ar--H).

EXAMPLE 4N,N-Dimethyl-2-[5-(1-methyltetrazol-5-ylmethyl)-1H-indol-3-yl]ethylamine.Oxalate

Prepared from2-[5-(1-methyltetrazol-5-ylmethyl)-1H-indol-3-yl]ethylamine (0.125 g,0.49 mmol) using the procedure described in step 3, Example 3. The freebase (0.11 g, 80%) obtained was converted to the oxalate salt andrecrystallised from MeOH/Et₂ O; mp 176°-177° C.; (Found: C, 54.21; H,5.84; N, 22.36. C₁₅ H₂₀ N₆. C₂ H₂ O₄ requires C, 54.54; H, 5.92; N,22.45%); δ (360 MHz, D₂ O); 2.91 (6H, s, 2 of CH₃); 3.21 (2H, t, J=7.4Hz, CH₂); 3.40 (2H, t, J=7.4 Hz, CH₂); 4.00 (3H, s, CH₃); 4.43 (2H, s,CH₂); 7.13 (1H, dd, J=1.5 and 8.4 Hz, Ar--H); 7.35 (1H, s, Ar--H); 7.50(1H, d, J=8.4 Hz, Ar--H); 7.54 (1H, s, Ar--H).

EXAMPLE 5N,N-Dimethyl-2-[5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl]ethylamine.Oxalate Hemihydrate

1. 1-(4-Nitrophenyl)methyl-1,2,4-triazole

4-Nitrobenzylbromide (21.6 g, 0.1 mol) was added to a rapidly stirredsuspension of 1,2,4-triazole sodium salt (9.1 g, 0.1 mol) in anhydrousDMF (100 ml) and the mixture stirred at room temperature for 16 h. Ethylacetate (400 ml ) was added followed by water (250 ml) and the layersseparated. The organic phase was washed with water (3×250 ml), dried(MgSO₄) and evaporated. The residue was chromatographed on silica geleluting with ethyl acetate to give the title-product (10.6 g, 52%); m.p.98°-100° C. δ (360 MHz, CDCl₃) 5.47 (2H, s, CH₂) 7.40 (2H, d, J=9 Hz,Ar--H), 8.02 (1H, s, Ar--H), 8.18 (1H, s, Ar--H), 8.23 (2H, d, J=9 Hz,Ar--H).

2. 1-(4-Aminophenyl)methyl-1,2,4-triazole. Hydrochloride

A solution of 1-(4-nitrophenyl)methyl-1,2,4-triazole (10.0 g, 49 mmol)in ethanol (50 ml), ethyl acetate (50 ml), 5N HCl (10 ml) and water (10ml) was hydrogenated over 10% Pd/C (1.0 g) at 40 p.s.i., in a Parrapparatus, until an uptake of 188 p.s.i., had been observed (approx 10mins). The catalyst was removed by filtration through hyflo and thesolvent removed under vacuum. The residue was azeotroped with ethanol(×2) to give the title-amine hydrochloride (10.6 g, 100%). δ (360 MHz,D₂ O) 5.53 (2H, s, CH₂), 7.37-7.48 (4H, m, Ar--H), 8.12 (1H, s, Ar--H),8.66 (1H, s, Ar--H).

3. 1-(4-Hydrazinophenyl)methyl-1,2,4-triazole

A solution of sodium nitrite (3.28 g, 48 mmol) in water (20 ml) wasadded to a solution of the preceding amine hydrochloride (10.0 g, 48mmol), in concentrated HCl (40 ml), at such a rate that the temperaturedid not exceed -10° C. After addition was complete the solution wasstirred at 0° C. for 0.25 h and then added portionwise to a rapidlystirred solution of SnCl₂.2H₂ O (40 g) in concentrated HCl (40 ml). Thesolution was warmed to room temperature and basified with 20% aqueousNaOH solution. The solution was extracted with ethyl acetate (3×250 ml)and the combined extracts dried (MgSO₄) and filtered through hyflo. Thesolution was evaporated to dryness to give the desired hydrazine (5.0 g,56%) m.p. 109°-112° C. δ (360 MHz, D₆ -DMSO) 3.93 (2H, br s, NH₂), 5.20(2H, s, CH₂), 6.73 (2H, d, J=8 Hz, Ar--H), 7.08 (2H, d, J=8 Hz, Ar--H),7.92 (1H, s, Ar--H), 8.57 (1H, s, Ar--H).

4. 2-[5-(1,2,4-Triazol-1-ylmethyl)-1H-indol-3-yl]ethylsmine.

4-Chlorobutanal dimethylacetal (3.22 g, 21.1 mmol) was added to astirred solution of the preceding hydrazine (5.0 g, 26.4 mmol) inethanol/water (5:1, 180 ml) and 5N HCl (4.5 ml) and the solutionrefluxed for 4 h. The solvents were removed under vacuum and the residuechromatographed on silica gel, eluting with CH₂ Cl₂ /EtOH/NH₃ (30:8:1)to give the desired tryptamine (2.4 g, 38%). δ (360 MHz, CDCl₃) 2.90(2H, t, J=7 Hz, CH₂), 2.99 (2H, t, J=7 Hz, CH₂), 5.43 (2H, s, CH₂), 7.10(1H, s, Ar--H), 7.11 (1H, d, J=8 Hz, Ar--H), 7.39 (1H, d, J=8 Hz,Ar--H), 7.57 (1H, s, Ar--H), 7.94 (1H, s, Ar--H), 8.08 (1H, s, Ar--H).

5. N,N-Dimethyl-2-[5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl]ethylamineOxalate Hemihydrate

A solution of formaldehyde (37% w/w solution, 0.19 g), in methanol (10ml), was added to a mixture of the preceding tryptamine (0.36 g, 1.5mmol), NaCNBH₃ (0.225 g, 3.6 mmol) and glacial acetic acid (0.45 g), inmethanol (10 ml). The mixture was stirred at room temperature for 2 hbefore adding saturated K₂ CO₃ (50 ml) and evaporating the methanol. Theresidue was extracted with ethyl acetate (3×100 ml) and the combinedextracts washed with brine (100 ml), dried (K₂ CO₃), and evaporated. Thecrude product was chromatographed on silica gel eluting with CH₂ Cl₂/EtOH/NH₃ (20:8:1) to give the free base of the title-compound (0.21 g,52%). The oxalate hemihydrate salt was prepared, m.p. 165°-167° C.(MeOH/Et₂ O); (Found: C, 55.53; H, 6.04; N, 18.59. C₁₅ H₁₉ N₅.C₂ H₂ O₄.0.55H₂ O requires C, 55.29; H, 6.03; N, 18.96%); m/e 269 (M⁺); δ5 (360MHz, D₂ O) 2.91 (6H, s, NMe₂), 3.22 (2H, t, J=7 Hz, CH₂), 3.47 (2H, t,J=7 Hz, CH₂), 5.52 (2H, s, CH₂), 7.21 (1H, dd, J=1.6 and 8.4 Hz, Ar--H),7.36 (1H, s, Ar--H), 7.52 (1H, d, J=8.4 Hz, Ar--H), 7.65 (1H, s, Ar--H),8.06 (1H, s, Ar--H), 8.56 (1H, s, Ar--H).

EXAMPLE 6N,N-Dimethyl-2-[5-(1,2,3,4-tetrazol-2-ylmethyl)-1H-indol-3-yl]ethylamineOxalate

1. 1-(4-Nitrophenyl)methyl-1,2,3,4,-tetrazole and2-(4-nitrophenyl)methyl-1,2,3,4-tetrazole.

4-Nitrobenzylbromide (15.42 g, 71.3 mmol) was added to a stirredsolution of 1H-tetrazole (5.0 g, 71.3 mmol) and triethylamine (7.9 g,78.0 mmol) in acetonitrile (100 ml). The mixture was stirred at roomtemperature for 16 h, the solvent removed under vacuum and the residuechromatographed on silica gel eluting with dichloromethane to give2-isomers. The 2-alkylated product was obtained as the less polarproduct (2.47 g, 17%); δ (360 MHz, CDCl₃) 5.92 (2H, s, CH₂), 7.53 (2H,d, J=8.7 Hz, Ar--H), 8.25 (2H, d, J=8.7 Hz, Ar--H), 8.56 (1H, s, Ar--H).The more polar, major isomer was identified as the 1-alkylation product(11 g, 75%); δ (360 MHz, CDCl₃) 5.73 (2H, s, CH₂), 7.46 (2H, d, J=8.7Hz, Ar--H), 8.27 (2H, d, J=8.7 Hz, Ar--H), 8.64 (1H, s, Ar--H).

2. 2-(4-Aminophenyl)methyl-1,2,3,4-tetrazole. Hydrochloride

2-(4-Nitrophenyl)methyl-1,2,3,4-tetrazole (2.47 g, 12.1 mmol) washydrogenated as described for Example 5 step 2. The product (2.55 g,100% ) was obtained as the hydrochloride salt; δ (250 MHz, D₂ O) 5.86(2H, s, CH₂), 7.40 (2H, d, J=8.7 Hz, Ar--H), 7.36 (2H, d, J=8.7 Hz,Ar--H), 8.74 (1H, s, Ar--H).

3.N,N-Dimethyl-2-[5-(1,2,3,4-tetrazol-2-ylmethyl)-1H-indol-3-yl]ethylamine.Oxalate.

The preceding amine was converted into the title-compound using thegeneral procedures described for Example 5 Steps 3-5.The oxalate saltwas prepared and recrystallised from MeOH/Et₂ O; mp 198°-199° C.;(Found: C, 53.38; H, 5.55; N, 22.63. C₁₄ H₁₈ N₆. C₂ H₂ O₄. 0.2 (EtOH)requires C, 53.30; H, 5.78; N, 22.74%); δ (360 MHz, D₂ O) 2.91 (6H, s,NMe₂), 3.23 (2H, t, J=7.4 Hz, CH₂), 3.48 (2H, t, J=7.4 Hz, CH₂), 6.01(2H, s, CH₂), 7.30 (1H, dd, J=1.6 and 8.4 Hz, Ar--H), 7.37 (1H, s,Ar--H), 7.53 (1H, d, J=8.4 Hz, Ar--H), 7.76 (1H, s, Ar--H), 8.74 (1H, s,Ar--H).

EXAMPLE 7N,N-Dimethyl-2-[5-1,2,3,4-tetrazol-1-ylmethyl)-1H-indol-3-yl]ethylamine.Succinate

1-(4-nitrophenyl)methyl-1,2,3,4-tetrazole was converted into thetitle-compound using the procedures described for Example 5. Thesuccinate salt was prepared, m.p. 55°-56° C. (isopropylalcohol); (FoundC: 57.08; H, 6.14; N, 23.34. C₁₄ H₁₈ N₆. 0.75 (C₄ H₆ O₄) requires C,56.89; H, 6.32; N, 23.42%); δ (360 MHz,D₂ O) 2.93 (6H, s, NMe₂), 3.23(2H, t, J=7.5 Hz, CH₂), 3.48 (2H, t, J=7.5 Hz, CH₂), 5.81 (2H, s, CH₂),7.28 (1H, dd, J=1.7 and 8.4 Hz, Ar--H), 7.39 (1H, s, Ar--H), 7.56 (1H,d, J=8.4 Hz, Ar--H), 7.75 (1H, s, Ar--H), 9.20 (1H, s, Ar--H).

EXAMPLE 8N,N-Dimethyl-2-[5-(1-methyl-1,2,4-trazol-5-ylmethyl)-1H-indol-3-yl]ethylamine.Bisoxalate

1. Ethyl 3-[2-(dimethylamino)ethyl]-1H-indole-5-methylcarboximidate.Hydrochloride

A solution of N,N-dimethyl-2-(5-cyanomethyl-1H-indol-3-yl)ethylamine (5g, 22.01 mmol) in ethanol was saturated with HCl gas and the solutionstirred at room temperature for 16 h. The solvent was removed .undervacuum to give the title-product (6 g, 92%); δ (360 MHz, D₆ -DMSO) 1.29(3H, t, J=7.0 Hz, CH₂); 2.83 (6H, s, NMe₂), 3.13 (2H, t, J=7.5 Hz, CH₂),3.31 (2H, m, CH₂), 4.04 (2H, s, CH₂), 4.42 (2H, q, J=7.0 Hz, CH₂), 7.08(1H, dd, J=1.5 and 8.4 Hz, Ar--H), 7.27 (1H, s, Ar--H), 7.37 (1H, d,J=8.4 Hz, Ar--H), 7.48 (1H, br s, NH), 7.71 (1H, s, Ar--H).

2.N,N-Dimethyl-2-[5-(1-methyl-1-2,4-triazol-5-ylmethyl)-1H-indol-3-yl]ethylamine.Bisoxalate

A mixture of the preceding imidate ester (3 g, 10.15 mmol),methylhydrazine (0.8 ml) and triethylamine (3.54 ml), in ethanol (30ml), was stirred at room temperature for 3 h. The solvent was removedtrader vacuum and the resultant product dissolved in formic acid (98%,3.3 ml) and the solution stirred for 0.5 h at room temperature andrefluxed for 2 h. The solution was cooled to room temperature, pouredinto an aqueous solution of K₂ CO₃ (75 ml) and extracted with ethylacetate (4×200 ml). The combined extracts were dried (MgSO₄) andevaporated, and the residue chromatographed through silica gel elutingwith CH₂ Cl₂ /EtOH/NH₃ (40:8:1) to give 2-components. The less polarisomer was identified as the title-1-methyl-1,2,4-triazole (360 mg). Thebisoxalate salt was prepared; mp 135°-137° C.; (Found: C, 50.91; H,5.38; N, 13.86. C₁₆ H₂₁ N₅. 0.25(ethanol) requires C, 50.70; H, 5.47; N,14.08%); δ (360 MHz, D₂ O) 2.91 (6H, s, NMe₂); 3.23 (2H, t, J=7.3 Hz,CH₂), 3.48 (2H, t, J=7.3 Hz, CH₂), 3.95 (3H, s, Me), 4.48 (2H, s, CH₂),7.13 (1H, dd, J=1.5 and 8.4 Hz, Ar--H), 7.37 (1H, s, Ar--H), 7.53 (1H,d, J=8.4 Hz, Ar--H), 7.57 (1H, s, Ar--H), 8.32 (1H, s, Ar--H).

EXAMPLE 9 N,N-Dimethyl-2-[5-(1-methyl-1,2,4-triazol-3-ylmethyl)-1H-indol-3-yl]ethylamine. Trishydrochloride

The more polar isomer obtained from Example 8 Step 2 was identified asthe title-triazole (180 mg). The trishydrochloride salt was prepared, mp<40° C. (hygroscopic); Found: C, 49.80, H, 6.56; N, 16.69. C₁₆ H₂₁ N₅.3HCl. 0.35 (Et₂ O) requires C, 49.91; H, 6.62; N, 16.73%); δ (360 MHz,D₂ O) 2.91 (6H, s, NMe₂); 3.23 (2H, t, J=7.4 Hz, CH₂), 3.49 (2H, t,J-7.4 Hz, CH₂), 3.95 (3H, s, Me), 4.27 (2H, s, CH₂), 7.17 (1H, dd, J=1.5and 8.5 Hz, Ar--H), 7.34 (1H, s, Ar--H), 7.50 (1H, d, J=8.5 Hz, Ar--H),7.60 (1H, s, Ar--H), 8.88 (1H, s, Ar--H).

EXAMPLE 10N,N-Dimethyl-2-[5-(1,2,3-triazol-ylmethyl)-1H-indol-3-yl]ethylamine.Oxalate

1. 1-(4-nitrophenyl)methyl-1,2,3-triazole

4-Nitrobenzylbromide (25.4 g, 0.12 mol) was added to a solution of1H-1,2,3-triazole (8.12 g, 0.12 mol) and triethylamine (11.88 g, 0.12mol) in anhydrous acetonitrile. The mixture was refluxed for 1 h, cooledto room temperature and the precipitated NEt₃. HBr filtered off. Thesolvent was removed under vacuum and the residue chromatographed throughsilica gel eluting with CH₂ Cl₂ (100) to CH₂ Cl₂ /MeOH (95.5) to give2-products. The more polar product was identified as the title-1-isomer(13 g, 54%); mp 114°-116° C. δ (250 MHz, CDCl₃) 5.72 (2H, s, CH₂), 7.38(2H, d, J=9 Hz, Ar--H), 7.64 (1H, s, Ar--H), 7.78 (1H, s, Ar--H), 8.18(2H, d, J=9 Hz, Ar--H). The less polar, minor isomer was identified asthe 2-alkylation product (2.25 g, 9%), mp 112°-113° C. δ (250 MHz,CDCl₃) 5.72 (2H, s, CH₂), 7.40 (2H, d, J=9 Hz, At--H), 7.66 (2H, s,Ar--H), 8.18 (2H, d, J=9 Hz, Ar--H).

2.N,N-Dimethyl-2-[5-(1,2,3-triazol-1-ylmethyl)-1H-indol-3-yl]ethylamine.Oxalate 1-(4-nitrophenyl)methyl-1,2,3-triazole was converted into thetitle-indole using the general procedures described for example 5.Theoxalate salt was prepared mp 210°-212° C., (Found: C, 55.88; H, 5.75; N,18.69. C₁₅ H₁₉ N₅. 1.1(C₂ H₂ O₄) 0.15H₂ O requires C, 55.67; H, 5.84; N,18.87%), δ (360 MHz, D₂ O). 2.90 (6H, s, NMe₂), 3.22 (2H, t, J=7.4 Hz,CH₂), 3.46 (2H, t, J-7.4 Hz, CH₂), 5.72 (2H, s, CH₂), 7.24 (1H, dd,J=1.6 and 8.4 Hz, Ar--H), 7.36 (1H, s, Ar--H), 7.52 (1H, d, J=8.4 Hz,Ar--H), 7.66 (1H, s, Ar--H), 7.79 (1H, s, Ar--H), 8.00 (1H, d, J=1 Hz,Ar--H)

EXAMPLE 11 3-(2-Aminoethyl)-5-(2-methyl-tetrazol-5-yl)benzo[b]thiophene.Oxalate

Step 1

4-Bromonphenylmercaptopropanone

To a stirred solution of 4-bromothiophenol (5.09 g, 6.9 mmol) in NaOH(1.08 g, 26.9 mmol) and water (32 ml) was added chloroacetone (2.17 ml,27.3 mmol) and the mixture was stirred under nitrogen for 45 min beforeextracting with ether, washing with water, drying (Na₂ SO₄) andevaporating in vacuo, leaving 6.89 g (100%) of the title compound as awhite solid, δ (CDCl₃) 2.27 (3H, s), 3.65 (2H, s), 7.20 (2H, d, J=8.5Hz), 7.41 (2H, d, J=8.5 Hz).

Step 2

5-Bromo-3-methyl benzo[b)]thiophene

To a gently refluxing mixture of polyphosphoric acid (4.47 g) andchlorobenzene (100 ml) was added 4-bromophenylmercaptopropanone (2.24 g,9.14 mmol) portionwise over 1 h and the mixture was heated at reflux for8 days. After cooling the organic phase was decanted off and the residuewas decomposed with H₂ O (˜100 ml), extracted with CH₂ CI₂ (2×75 ml),dried (MgSO₄) and combined with the decanted organic phase. This wasevaporated in vacuo to leave 2.096 g of brown oil. Distillation on aKugelrohr apparatus yielded 1.83 g (88%) of the title compound as a paleyellow liquid, bp 100°-110° C./0.35 mbar. δ (CDCl₃) 2.41 (3H, s), 7.10(1H, s), 7.43 (1H, dd, J=8.5 and 1.9 Hz), 7.69 (1H, d, J=8.5 Hz), 7.64(1H, d, J=1.9 Hz).

Step 3

5-Cyano-3-methyl benzo[b]thiophene

To copper (I) cyanide (0.569 g, 6.35 mmol) was added 5-bromo-3-methylbenzo[b]thiophene (1.179 g, 5.19 mmol) in N-methylpyrrolidinone (10 ml)and the mixture was stirred at 180°-90° C. for 17 h. This was thenpartitioned between ether (75 ml) and ammonia solution (75 ml). Theether layer was separated, washed with more ammonia solution (2×50 ml),dried (Na₂ SO₄) and evaporated in vacuo to leave 0.81 g of an off-whitesolid. Chromatography on flash silica, eluting with 10% ethylacetate/petroleum ether yielded 0.76 g (85%) of the title compound as awhite solid. δ (CDCl₃) 2.47 (3H, s), 7.23 (1H, s), 7.55 (1H, dd, J=8.3and 1.5 Hz), 7.93 (1H, d, J=8.4 Hz), 8.03 (1H, d, J=1.4 Hz).

Step 4

3-Methyl-5-(tetrazol-5-yl)-benzo[b]thiophene

To a solution of 5-cyano-3-methyl benzo[b]thiophene (0.194 g, 1.12 mmol)in N-methylpyrrolidinone (5 ml) under nitrogen was added triethylaminehydrochloride (0.231 g, 1.68 mmol) followed by sodium azide (0.234 g,3.59 mmol) and the mixture was extracted with ether (4×50 ml). Thecombined ether extracts were dried (Mg SO₄) and evaporated in vacuo toleave 0.78 g of a white solid. This was chromatographed on flash silica,eluting with CH₂ CI₂ /MeOH/NH₃ (aq) (40:8:1 to 30:8:1), to give 0.246 g(100%) of the title product as a white solid. δ (DMSO) 2.46 (3H, s),7.41 (1H, s), 7.98 (1H, d, J=8.4 Hz), 8.03 (1H, dd, J=8.4 and 1.5 Hz),8.36 (1H, d, J=0.9 Hz). m/z (CI⁻, NH₃) 215 (M-H)⁻, 160.

Step 5

3-Methyl-5-(2-methyltetrazol-5-yl )benzo[b]thiophene and3-Methyl-5-(1-methyltetrazol-5-yl)benzo[b]thiophene

To a mixture of 3-Methyl-5-(tetrazol-5-yl)benzo[b]thiophene (0.241 g,1.12 mmol) in acetonitrile (5 ml) was added triethylamine (0.28 ml ,2.01 mmol), then iodomethane (0.486 ml , 7.81 mmol) followed by DMF (3ml) until a clear solution formed. The solution was stirred overnightunder nitrogen before evaporating in vacuo and partitioning the residuebetween water (50 ml) and ether (25 ml). The aqueous layer was separatedand extracted with more ether (2×25 ml), the combined ether extractswere dried (Mg SO₄) and evaporated in vacuo to leave 0.241 g of yellowsolid. Chromatography on flash silica, eluting with 25-40% ethylacetate/petroleum ether gave 0.168 g (65%) of the 2-isomer of the titleproduct as a white solid and 0.063 g (24%) of the 1-isomer of the titleproduct as a white solid. 2-isomer δ (CDCl₃) 2.52 (3H, s), 4.42 (3H, s),7.14 (1H, s), 7.94 (1H, d, J=8.4 Hz), 8.10 (1H, dd, J=8.4 and 1.5 Hz),8.51 (1H, s). m/z (CI⁺, NH₃) 231 (M+H)⁺ 1-isomer δ (CDCl₃) 2.50 (3H, s),4.22 (3H, s), 4.22 (3H, s), 7.23 (1H, s), 7.64 (1H, dd, J=8.3 and 1.5Hz), 8.03 (1H, d, J=8.4 Hz), 8.12 (1H, d, J=1.6 Hz). m/z (CI⁺, NH₃) 231(M+H)⁺, 202, 172.

Step 6

3-Cyanomethyl-5-(2-methyltetrazol-5-yl)benzo[b]thiophene

To a refluxing mixture of 3-methyl-5-(2-methyltetrazol-5yl)benzo[b]thiophene (0.162 g, 0.703 mmol) and benzoyl peroxide (10.6 mg)in carbon tetrachloride (10 ml) irradiated with two desk lamps (2×60W)was added. N-bromosuccinimide (0.126 g, 0.707 mmol) in small portions.After the addition was complete the mixture was heated at reflux for afurther 90 min, then filtered and the filtrate was evaporated in vacuoto leave an oil/solid mixture. Chromatography on flash silica, elutingwith dichloromethane gave 0.161 g of crude3-bromomethyl-5-(2-methyltetrazol-5-yl) benzo[b]thiophene as acolourless off.

The crude 3-bromomethyl-5-(2-methyl-tetrazol-5-yl)benzo[b]thiophene(0.145 g) in DMSO (0.3 ml) was added to a mixture of sodium cyanide(29.9 mg, 0.6 mmol) in DMSO (0.2 ml) and the mixture was stirred at 100°C. for 2 h. After cooling, the mixture was poured into water (10 ml) anda brown solid was filtered off, washed with water and dried in a vacuumpistol to leave 73.5 mg. The filtrate was extracted with dichloromethane(3×30 ml) and the combined extracts were dried (Na₂ SO₄) and evaporatedin vacuo to leave 44.7 mg. This was combined with the original solid andchromatographed on flash silica, eluting with 20-50% ethylacetate/petroleum ether to yield 61.5 mg (38%) of the title product as awhite solid. δ (CDCl₃) 3.99 (2H, s), 4.43 (3H, s), 7.59 (1H, s), 8.00(1H, d, J=8.5 Hz), 8.19 (1H, dd, J=8.5 and 1.5 Hz), 8.47 (1H, s).

Step 7

3-(2-Aminoethyl)-5-(2-methyl-tetrazol-5-yl)benzo[b]thiophene. Oxalate.

To a solution of3-cyanomethyl-5-(2-methyl-tetrazol-5-yl)benzo[b]thiophene (0.434 g, 1.70mmol) in THF (16 ml) under nitrogen was added dropwise 1.0Mborane-tetrahydrofuran complex in THF (5.10 ml , 5.10 mmol) and themixture was heated at reflux for 6 h. After cooling in an ice-bath themixture was quenched with 2N HCl (22 ml) and heated to reflux for 1 h.The THF was then removed in vacuo and the residue basified with 50%sodium hydroxide solution (4 ml) before extracting with dichloromethane(3×75 ml). The combined extracts were dried (K₂ CO₃) and evaporated invacuo to leave 0.45 g. Chromatography on flash silica eluting with CH₂Cl₂ /MeOH/NH₃ (aq) (60:8:1) gave 0.383 g (87%) of the title product as awhite solid. The oxalate salt was prepared using oxalic acid inmethanol/ether to give the title product oxalate as a white solid, m.p.204°-209° C. Analysis found: C, 47.75; H, 4.28; N, 19.28%. Calcd for C₁₂H₁₃ N₅ S. 1.1 C₂ H₂ O₄ : C, 47.59; H, 4.28; N, 19.54%. δ (DMSO)3.17-3.21 (4H, m), 4.46 (3H, s), 7.72 (1H, s), 8.06 (1H, dd, J=8.4 and1.4 Hz), 8.52(1H, s) m/z (CI⁺, NH₃) 260 (M+H)⁺, 230.

EXAMPLE 12 3-(2-Aminoethyl)-5-(1-methyltetrazol-5-yl)benzo[b]thiophene.Oxalate

Step 1

3-Cyanomethyl-5-(1-methyltetrazol-5-yl)benzo[b]thiophene

Following the procedure of Example 11, Step 6, 0.666 g (2.89 mmol)3-methyl-5-(1-methyltetrazol-5-yl)benzo[b]thiophene was reacted with0.515 g (2.89 mmol) of N-bromosuccinimide and 38.1 mg of benzoylperoxide in 30 ml of carbon-tetrachloride. The reaction mixture wasevaporated in vacuo and chromatographed on flash silica, eluting with0-3% methanol/dichloromethane to give 0.532 g of crude3-bromo-5-(1-methyltetrazol-5-yl) benzo[b]thiophene.

The crude 3-bromo-5-(1-methyltetrazol-5-yl)benzo[b]thiophene (0.504 g)was reacted with 97.7 mg (1.99 mmol) of sodium cyanide in 1.5 ml of DMSOat 100° C. for 2 h. After cooling, the reaction mixture was poured intowater (25 ml) and extracted with dichloromethane (6×50 ml). The combinedextracts were dried (Na₂ SO₄) and evaporated in vacuo to leave 0.37 g.Chromatography on flash silica, eluting with 30-60% ethylacetate/petroleum ether yielded 28.0 mg (4%) of the title product. δ(CDCl₃) 4.00 (2H, s), 4.23 (3H, s), 7.63 (1H, s), 7.73 (1H, dd), 8.08(1H, d), 8.15 (1H, d).

Step 2

3-(2-Aminoethyl)-5-(1-methyltetrazol-5-yl)benzo[b]thiophene. Oxalate.

Following the procedure of Example 11, Step 7, 26.1 mg (0.102 mmol) of3-cyanomethyl-5-(1-methyltetrazol-5-yl)benzo[b]thiophene in 2 ml of THFwas reacted with 0.36 ml (0.36 mmol) of 1.0M borane-tetrahydrofurancomplex in THF. Chromatography on flash silica, eluting with CH₂ Cl₂/MeOH/NH₃ (aq) (60:8:1) gave 17.7 mg (67%) of the title product as acolourless oil. The oxalate salt was prepared using oxalic add inmethanol/ether to give the title product oxalate as a white solid, m.p.206°-212° C. Analysis found: C, 47.55; H, 4.05; N, 19.65%. Calcd for C₁₂H₁₃ N₅ S. 1.1 C₂ H₂ O₄ : C, 47.59; H, 4.28; N, 19.54%. δ (D₂ O)3.32-3.35 (2H, m), 3.40-3.44 (2H, m), 4.22 (3H, s), 7.64 (1H, s), 7.73(1H, d, J=8.4 Hz), 8.19 (1H, s), 8.22 (1H, d, 8.5 Hz).

EXAMPLE 133-[2-(N,N-Dimethylamino)ethyl]-5-(2-methyltetrazol-5-yl)benzo[b]thiophene.Oxalate

To a mixtureof-(2-aminoethyl)-5-(2-methyltetrazol-5-yl)benzo[b]thiophene (0.372 g,1.43 mmol) and sodium cyanoborohydride (0.136 g, 2.15 mmol) in methanol(3 ml) and acetic acid (0.247 ml, 4.30 mmol) cooled in an ice bath wasadded 38% w/v formaldehyde solution (0.453 ml , 5.74 mmol) in methanol(3 ml) dropwise over 5 min and the mixture was stirred at roomtemperature for 3 h. After this time, saturated potassium carbonatesolution (30 ml) was added and the mixture was extracted with ethylacetate (3×50 ml). The combined o extracts were evaporated in vacuo toleave 0.53 g. Chromatography on flash silica, eluting with 10-30%methanol/dichloromethane, gave 0.335 g (81%) of the title product as acolourless oil. The oxalate salt was prepared using oxalic acid inmethanol/ether to give the title product oxalate as a white solid, m.p.214°-218° C. Analysis found: C, 50.58; H, 4.80; N, 18.28%. Calcd for C₁₄H₁₇ N₅ S. C₂ H_(204:) C, 50.92; H, 5.07; N, 18.56%. δ (DMSO) 2.84 (6H,s), 3.30-3.42 (4H, m), 4.46 (3H, s), 7.69 (1H, s), 8.06 (1H, dd, J=8.4and 1.4 Hz), 8.20 (1H, d, J=8.4 Hz), 8.56 (1H, s). m/z (CI⁺, NH₃) 288(M+H)⁺.

EXAMPLE 14N,N-Dimethyl-2-[5-(2-methylimidazol-1-ylmethyl)-1H-indol-3-yl]ethylamineTrisoxalate

1.1-(4-Nitrophenyl)methyl-2-methylimidazole

Sodium hydride (2.45 g; 61.0 mmol, 60% dispersion in oil) was added to asolution of 2-methylimidazole (5.0 g, 60.9 mmol) in DMF (100 ml). Themixture was stirred at room temperature for 0.25 h before adding4-nitrobenzyl bromide (13.2 g, 61.0 mmol) and heating at 110° C. for 2 hfollowed by stirring at room temperature for 16 h. Water (200 ml) andethyl acetate (500 ml) were added, the aqueous separated and extractedwith ethyl acetate (2×500 ml). The combined extracts were washed withwater (3×250 ml), dried (MgSO₄) and evaporated. The crude product waschromatographed on silica gel eluting with CH₂ Cl₂ /MeOH (4%) to givethe title-product (1.58 g, 10.5%); δ (360 MHz, CDCl₃) 2.34 (3H, s, Me);5.16 (2H, s, CH₂); 6.67 (1H, d, J=1.3 Hz, Ar--H); 7.03 (1H, d, J=1.3 Hz,Ar--H); 7.19 (2H, d, J=9.5 Hz, Ar--H); 8.22 (2H, d, J=9.5 Hz, Ar--H).

2. N,N-Dimethyl-2-[5-(2-methylimidazol-1-ylmethyl)-1H-indol-3-yl)ethylamine Trisoxalate

Prepared from the preceding 4-nitrobenzyl imidazole using the generalprocedure described for Example 5. The trisoxalate salt was prepared, mp160°-163° C. (MeOH/Et₂ O); (Found: C, 50.57; H, 5.25; N, 10.60. C₁₇ H₂₂N₄. 2.8 (C₂ H₂ O₄) requires C, 50.79; H, 5.21; N, 10.48%); m/e 282 (M⁺);δ (360 MHz, D₂ O) 2.65 (3H, s, Me); 2.92 (6H, s, NMe₂); 3.25 (2H, t,J=7.3 Hz, CH₂); 3.50 (2H, t, J=7.3 Hz, CH₂); 5.42 (2H, s, CH₂); 7.18(1H, d, J=8.4 Hz, Ar--H); 7.31-7.40 (2H, m, Ar--H); 7.40 (1H, s, Ar--H);7.56 (1H, d, J=8.4 Hz, Ar--H); 7.66 (1H, s, Ar--H).

EXAMPLE 15 N,N-Dimethyl-2-[5-imidazol-1-ylmethyl-1H-indol-3yl]ethylamineBisoxalate

Prepared from imidazole and 4-nitrobenzyl bromide using the proceduredescribed for Example 5. The bisoxalate salt was prepared, 165°-166° C.(MeOH/Et₂ O); (Found: C, 53.30; H, 5.34; N, 12.18. C₁₆ H₂₀ N₄. 2.05 (C₂H₂ O₄) requires C, 53.30; H, 5.36; N, 12.37%); δ (360 MHz, D₂ O) 2.92(6H, s, NMe₂); 3.24 (2H, t, J=7.7 Hz, CH₂); 3.48 (2H, t, J=7.7 Hz, CH₂);5.50 (2H, s, CH₂); 25 7.27 (1H, dd, J=1.5 and 8.4 Hz, Ar--H); 7.37 (1H,s, Ar--H); 7.45 (1H, s, Ar--H); 7.49 (1H, s, Ar--H); 7.56 (1H, d, J=8.4Hz, Ar--H); 7.75 (1H, s, Ar--H); 8.78 (1H, s, Ar--H).

EXAMPLE 16N,N-Dimethyl-2-[5-(2-methylimidazol-1-yl)-1H-indol-3-yl]ethylamineSesquioxalate

1. 1-(4-Nitrophenyl)-2-methylimidazole

Sodium hydride (4.87 g, 122.0 mmol, 60% dispersion in oil) was added toa solution of 2-methylimidazole (10 g, 122.0 mmol) in DMF (100 ml) andstirred at room temperature for 0.25 h. 1-Fluoro-4-nitrobenzene (17.18g, 122.0 mmol) was added to the reaction mixture and stirred at roomtemperature for 16 h. Water (150 ml) and ethyl acetate (250 ml) wereadded, the aqueous separated and extracted with ethyl acetate (3×150ml). The combined extracts were washed with water (3×150 ml), dried (Na₂SO₄) and evaporated to give the desired product (11.5 g, 47%); δ (360MHz, CDCl₃) 2.24 (3H, s, Me); 7.06 (1H, d, J=1.5 Hz, Ar--H); 7.10 (1H,d, J=1.5 Hz, Ar--H); 7.50 (2H, d, J=9.5 Hz, Ar--H); 8.38 (2H, d, J=9.5Hz, Ar--H).

2. N,N-Dimethyl-2-[5-(2-methylimidazol-1-yl)-1H-indol-3-yl]ethylamineSesquioxalate

Prepared from the preceding 4-nitrophenyl imidazole using the proceduredescribed for Example 5. The sesquioxalate salt was prepared, mp185°-186° C. (iPA/MeOH); (Found: C, 56.17; H, 5.99; N, 13.46.C₁₆ H₂₀ N₄.1.55 (C₂ H₂ O₄). 0.1 EtOH requires C, 56.19; H, 5.79; N, 13.58%); δ (360MHz, D₂ O) 2.55 (3H, s, Me); 2.93 (6H, s, NMe₂); 3.26 (2H, t, J=7.4 Hz,CH₂); 3.51 (2H, t, J=7.4 Hz, CH₂); 7.30 (1H, dd, J=2.0 and 8.7 Hz,Ar--H); 7.48 (1H, d, J=2.1 Hz, Ar--H); 7.51-7.53 (2H, m, Ar--H); 7.70(1H, d, J=8.7 Hz, Ar--H); 7.79 (1H, d, J=2.0 Hz, Ar--H).

EXAMPLE 17 N,N-Dimethyl-2-[5-(1,2,4- triazol-1-ylmethyl)-1H-indol-3-yl]ethylamine. Succinate. Procedure B

A solution of 1-(4-hydrazinophenyl)methyl-1,2,4-triazole dihydrochloride(2 g, 7.6 mmol, Example 5 step 3) and 4-N,N-dimethylaminobutanaldimethylacetal (1.8 g, 11.2 mmol) in 4% aqueous sulphuric acid (70 ml)was heated at reflux for 2 h. After the reaction mixture was cooled toroom temperature, ethyl acetate (200 ml) was added and the aqueousbasified with K₂ CO₃. The aqueous was separated and extracted furtherwith ethyl acetate (2×150 ml). The combined organics were dried (Na₂SO₄) and evaporated, and the residue chromatographed on silica geleluting with CH₂ Cl₂ /EtOH/NH₃ (30:8:1) to give the title-triazole (610mg, 30%). The succinate salt was prepared by addition of a solution ofsuccinic acid (0.27 g, 2.3 mmol) in methanol (3 ml) to a solution of thetriazole (0.61 g, 2.3 mmol) in methanol (5 ml). The solvent was removedunder vacuum and the resultant product recrystallised fromisopropylalcohol, mp 118°-120° C.; (Found: C, 58.76; H, 6.27; N, 17.79.C₁₅ H₁₉ N₃.C₄ H₆ O₄ requires C, 58.90; H, 6.50; N, 18.08%).

EXAMPLE 18 N,N-Dimethyl,2-[5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl]ethylamine. Benzoate

The benzoate salt ofN,N-dimethyl-2-[5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl]ethylaminewas prepared by addition of a solution of benzoic acid in diethyl etherto a solution of the free base in ethanol/diethyl ether (1:4). Theprecipitated salt was recrystallised from ethanol, mp 178°-180° C.;(Found: C, 67.28; H, 6.55; N, 17.66. C₁₅ H₁₉ N₃.C₆ H₅ CO₂ ^(H) requiresC, 67.50; H, 6.44; N, 17.89%); ¹ H NMR (360 MHz, D₂ O) δ2.92 (6H, s,NMe₂); 3.22 (2H, t, J=7.3 Hz, CH₂); 3.46 (2H, t, J=7.3 Hz, CH₂); 5.52(2H, s, CH₂); 7.22 (1H, dd, J=1.6 and 8.4 Hz, Ar--H); 7.36 (1H, s,Ar--H); 7.44-7.58 (4H, m, Ar--H); 7.65 (1H, s, Ar--H); 7.87-7.91 (2H, m,Ar--H); 8.06 (1H, s, Ar--H); 8.54 (1H, s, Ar--H).

EXAMPLE 19N,N-Dimethyl-2-[5-(2-ethyltetrazol-5-ylmethyl)-1H-indol-3-yl]ethylamine.Oxalate

Prepared as described for Example 3, using ethyl iodide. The oxalatesalt was prepared, mp 140°-142° C.; (Found: C, 55.71; H, 6.26; N, 21.35.C₁₆ H₂₂ N₆.C₂ H₂ O₄ requires C, 55.66; H, 6.23; N, 21.64%); ¹ H NMR (360MHz, D₂ O) δ 1.54 (3H, t, J=7.4 Hz, CH₃); 2.91 (6H, s, NMe₂); 3.21 (2H,t, J=7.4 Hz, CH₂); 3.47 (2H, t, J=7.4 Hz, CH₂); 4.34 (2H, s, CH₂); 4.64(2H, q, J=7.4 Hz, CH₂ CH₃); 7.17 (1H, dd, J=1.5 and 8.4 Hz, Ar--H); 7.33(1H, s, Ar--H); 7.48 (1H, d, J=8.4HZ, Ar--H); 7.59 (1H, s, Ar--H).

EXAMPLE 20N,N-Dimethyl-2-[5-(1-ethyltetrazol-5-ylmethyl)-1H-indol-3-yl]ethylamine.Oxalate

Prepared using the procedure described for Example 4, using ethyliodide. The oxalate salt was prepared, mp 179° C. (MeOH/Et₂ O); (Found:C, 55.59; H, 6.23; N, 21.49. C₁₆ H₂₂ N₆.C₂ H₂ O₄ requires C, 55.66; H,6.23; N, 21.64%); ¹ H NMR (360 MHz, D₂ O) δ1.32 (3H, t, J=7.4 Hz, CH₃);2.90 (6H, s, NMe₂); 3.21 (2H, t, J=7.4 Hz, CH₂); 3.46 (2H, t, J=7.4 Hz,CH₂); 4.38 (2H, q, J=7.4 Hz, CH₂); 4.47 (2H, s, CH₂); 7.14 (1H, dd,J=1.5 and 8.4 Hz, Ar--H); 7.35 (1H, s, Ar--H); 7.50 (1H, d, J=8.4 Hz,Ar--H); 7.53 (1H, s, Ar--H).

EXAMPLE 21N,N-Dimethyl-2-[5-(1,2,4-triazol-1-yl)-1H-indol-3-yl]ethylamine.Bisoxalate

Prepared as described for Example 16 from 1,2,4-triazole sodiumderivative and 1-fluoro-4-nitrobenzene. The bisoxalate salt wasprepared, mp 210° C. (MeOH/Et₂ O); (Found: C, 50.11; H, 4.78; N, 16.35.C₁₄ H₁₇ N₅. 1.9 (C₂ H₂ O ₄) requires C, 50.14; H, 4.92; N, 16.43%); ¹ HNMR (360 MHz, D₂ O) δ2.92 (6H, s, NMe₂); 3.25 (2H, t, J=7.4 Hz, CH₂);3.50 (2H, t, J=7.4 Hz, CH₂); 7.44 (1H, s, Ar--H); 7.47 (1H, dd, J=2.0and 8.7 Hz, Ar--H); 7.63 (1H, d, J=8.7 Hz, Ar--H); 7.88 (1H, d, J=2.0Hz, Ar--H); 8.36 (1H, s, Ar--H); 9.05 (1H, s, Ar--H).

EXAMPLE 224-[5-(2-Methylimidazol-1-yl)-1H-indol-3-yl]-N-methylpiperidine.Bisoxalate sesquihydrate

A solution of N-methyl-4-(formylmethyl)piperidine (0.25 g, 1.8 mmol) and4-(2-methylimidazolyl)phenyl hydrazine hydrochloride (0.48 g, 2.1 mmol)in 4% H₂ SO₄ (25 ml) was heated at reflux for 16 h. The mixture wascooled to room temperature, basified with K₂ CO₃ solution and extractedwith CH₂ Cl₂ (3×75 ml). The combined extracts were dried (Na₂ SO₄) andevaporated and the residue purified by chromatography on silica-geleluting with CH₂ Cl₂ /EtOH/NH₃ (60:8:1) to give the title-compound (0.12g). The bisoxalate sesquihydrate salt was prepared, mp 65°-70° C.(hygroscopic); (Found: C, 52.97; H, 5.51; N, 11.07. C₁₈ H₂₂ N₄.2(C₂ H₂O₄).1.5H₂ O requires C, 52.69; H, 5.83; N, 11.17%); ¹ H NMR (360 MHz, D₂O) δ1.96-2.08 (2H, m, CH₂); 2.31-2.40 (2H, m, CH₂); 2.56 (3H, s, CH₃);2.95 (3H, s, CH₃); 3.20-3.27 (3H, m, CH and CH₂); 3.64-3.68 (2H, m,CH₂); 7.28 (1H, dd, J=2 and 8.7 Hz, Ar--H); 7.44 (1H, s, Ar--H); 7.48(1H, d, J=2 Hz, Ar--H); 7.53 (1H, d, J=2 Hz, Ar--H); 7.69 (1H, d, J=8.7Hz, Ar--H); 7.81 (1H, d, J=2 Hz, Ar--H).

EXAMPLE 234-[5-(1,2,4-Triazol-1-ylmethyl)-1H-indol-3-yl]-N-methylpiperidine.Oxalate

A solution of N-methyl-4-(formylmethyl)piperidine (0.1 g, 0.71 mmol) and4-(1,2,4-triazolylmethyl)phenyl hydrazine dihydrochloride (0.185 g, 0.7mmol) in 4% H₂ SO₄ was heated at reflux for 2 h. The mixture was cooledto room temperature, basified with K₂ CO₃ solution and extracted withCH₂ Cl₂ (2×100 ml). The crude product was chromatographed on silica-geleluting with CH₂ Cl₂ /EtOH/NH₃ (40:8:1) to give the title-compound (60mg). The oxalate salt was prepared, mp 218°-220° C.; (Found: C, 58.61;H, 6.03; N, 17.94. C₁₇ H₂₁ N₅.1.02 (C₂ H₂ O₄) requires C, 58.96; H,6.38; N, 17.56%); ¹ H NMR (360 MHz, D₂ O) δ1.88-2.02 (2H, m, CH₂);2.20-2.34 (2H, m, CH₂); 2.92 (3H, s, CH₃); 3.10-3.24 (3H, m, CH andCH₂); 3.60-3.64 (2H, m, CH₂); 5.51 (2H, s, CH₂); 7.21 (1H, dd, J=1.5 and8.4 Hz, Ar--H); 7.26 (1H, s, Ar--H); 7.51 (1H, d, J=8.4 Hz, Ar--H); 7.69(1H, s, Ar--H); 8.05 (1H, s, Ar--H); 8.55 (1H, s, Ar--H).

EXAMPLE 24 1H-4-[5-(2-Methylimidazol-1-yl)-1H-indol-3-yl ]-piperidine.Bisoxalate dihydrate

1. 4-[5-(2-Methylimidazol-1-yl)-1H-indol-3-yl]-N-benzylpiperidine

Prepared from N-benzyl-4-(formylmethyl)pipeddine using the proceduredescribed for Example 22; ¹ H NMR (360 MHz, CDCl₃) δ1.80-1.94 (2H, m,CH₂); 1.98-2.06 (2H, m, CH₂); 2.14-2.24 (2H, m, CH₂); 2.33 (3H, s, CH₃);2.76-2.85 (1H, m, CH); 3.02-3.08 (2H, m, CH₂); 3.60 (2H, s, CH₂);7.03-7.10 (4H, m, Ar-H); 7.26-7.38 (5H, m, Ar--H); 7.41 (1H, d, J=8.5Hz, Ar--H); 7.52 (1H, d, J=1.8 Hz, Ar--H); 8.30 (1H, br s, NH).

2. 1H-4-[5-(2-Methylimidazol-1-yl)-1H-indol-3-yl]piperidine. Bisoxalatedihydrate

To a solution of ammonium formate (0.32 g, 5.07 mmol) and4-[5-(2-methylimidazol-1-yl)-1H-indol-3-yl]-N-benzylpipeddine (0.4 g,1.08 mmol), in methanol (40 ml) was added Pd/C (10%; 0.4 g) and themixture stirred at 60° C. for 3 h. The catalyst was removed byfiltration through celite and the solvent removed under vacuum. Theresidue was taken up into H₂ O (30 ml), basified with NH₃ solution andextracted with ethyl acetate (3×100 ml). The combined extracts weredried (Na₂ SO₄) and evaporated and the residue chromatographed throughsilica-gel eluting with CH₂ Cl₂ /MeOH/NH₃ (30:8:1) to give the desiredpiperidine (0.2 g). The bisoxalate dihydrate salt was prepared, mp 80°C. (hygroscopic); (Found: C, 50.53; H, 5.54; N, 10.87. C₁₇ H₂₀ N₄.2(C₂H₂ O₄).2.2H₂ O requires C, 50.43; H, 5.72; N, 11.20%); ¹ H NMR (360 MHz,D₂ O) δ1.91-2.03 (2H, m, CH₂); 2.30-2.34 (2H, m, CH₂); 2.55 (3H, s,CH₃); 3.19-3.36 (3H, m, CH and CH₂); 3.55-3.62 (2H, m, CH₂); 7.28 (1H,dd, J=1.2 and 8.6 Hz, Ar--H); 7.44 (1H, s, Ar--H); 7.47 (1H, d, J=2.0Hz, Ar--H); 7.52 (1H, d, J=2.0 Hz, Ar--H); 7.69 (1H, d, J=8.6 Hz,Ar--H); 7.82 (1H, d, J=1.2 Hz, Ar--H).

EXAMPLE 25 1H-4-[5-(1,2,4-Triazol-1-ylmethyl)-1H-indol-3-yl]piperidine.Oxalate

Prepared from N-benzyl-4-(formylmethyl)piperidine and4-(1,2,4-triazolylmethyl)phenyl hydrazine dihydrochloride using theprocedures described for Examples 23 and 24. The oxalate salt wasprepared, mp 272° C.; (Found: C, 58.27; H, 5.56; N, 18.79. C₁₆ H₁₉ N₅.C₂H₂ O₄ requires C, 58.21; H, 5.70; N, 18.86%); ¹ H NMR (360 MHz, D₂ O)δ1.86-1.98 (2H, m, CH₂); 2.24-2.28 (2H, m, CH₂); 3.15-3.36 (3H, m, CHand CH₂); 3.52-3.56 (2H, m, CH₂); 5.51 (2H, s, CH₂); 7.21 (1H, dd, J=1.6and 8.5 Hz, Ar--H); 7.27 (1H, s, Ar--H); 7.52 (1H, d, J=8.5 Hz, Ar--H);7.70 (1H, d, J=1.6 Hz, Ar--H); 8.09 (1H, s, Ar--H); 8.60 (1H, s, Ar--H).

EXAMPLE 26 1H-3-[5-(2-Methylimidazol-1-yl)-1H-indol-3-yl]-pyrrolidine.Bisoxalate

1. 3-[5-(2-Methylimidazol-1-yl)-1-H-indol-3-yl]-N-benzylpyrrolidine

Prepared from N-benzyl-3-(formylmethyl)pyrrolidine and4-(2-methylimidazolyl)phenyl hydrazine hydrochloride as described forExample 22; 1H NMR (360 MHz, CDCl₃) δ1.98-2.06 (1H, m, CH of CH₂); 2.34(3H, s, CH₃); 2.34-2.44 (2H, m, 2 of CH of CH₂); 2.71 (1H, t, J=7.4 Hz,CH of CH₂); 2.80 (1H, t, J=6.9 Hz, CH of CH₂); 3.05 (1H, t, J=8.7 Hz, CHof CH₂) 3.61-3.73 (1H, m, CH); 3.72 (2H, ABq, J=13 Hz, CH₂); 6.95-7.14(4H, m, Ar--H); 7.22-7.41 (5H, m, Ar--H); 7.40 (1H, d, J=8.5 Hz, Ar--H);7.66 (1H, s, Ar--H); 8.30 (1H, br s NH).

2. 1H-3-[5-(2-Methylimidazol-1-yl)-1H-indol-3-yl]-pyrrolidine.Bisoxalate

Prepared from the preceding N-benzylpyrrolidine using the proceduredescribed for Example 24. The bisoxalate salt was prepared, mp 210°-213°C. (methanol/ether); (Found: C, 53.93; H, 5.22; N, 12.50. C₁₆ H₁₈ N₄.2(C₂ H₂ O₄) requires C, 53.81; H, 4.97; N, 12.55%); ¹ H NMR (360 MHz, D₂O) δ2.91-2.30 (1H, m, CH of CH₂); 2.55 (3H, s, CH₃); 2.55-2.60 (1H, m,CH of CH₂); 3.35-3.64 (3H, m, CH and CH₂); 3.80-3.90 (2H, m, CH₂); 7.30(1H, dd, J=2 and 8.6 Hz, Ar--H); 7.47 (1H, d, J=2 Hz, Ar--H); 7.50 (1H,s, Ar--H); (7.53 (1H, d, J=2 Hz, Ar--H); 7.70 (1H, d, J=8.6 Hz, Ar--H);7.80 (1H, d, J=2 Hz, Ar--H).

EXAMPLE 27N-Methyl-3-[5-(2-methylimidazol-1-yl)-1H-indol-3-yl]pyrrolidine.Bisoxalate

To a cooled (0° C.), stirred mixture of1H-3-[5-(2-methylimidazol-1-yl)-1H-indol-3-yl]pyrrolidine (0.12 g, 0.45mmol), acetic acid (0.136 g, 2.3 mmol) and NaCNBH₃ (71 mg, 1.1 mmol), inmethanol (15 ml), was added dropwise a solution of formaldehyde (89 mgof a 38% w/w solution in H₂ O, 1.1 mmol) in methanol (10 ml). Themixture was stirred at 0° C. for 0.1 h before warming to roomtemperature and stirring for 1.5 h. Saturated K₂ CO₃ solution (10 ml)was added and the solvent removed under vacuum. The residue wasextracted with ethyl acetate (3×100 ml) and the combined extracts dried(Na₂ SO₄) and evaporated. The crude product was chromatographed onsilica-gel eluting with CH₂ Cl₂ /MeOH/NH₃ (60:8:1) to give the titleproduct (0.1 g). The bisoxalate salt was prepared, mp 191°-194° C.(MeOH/Et₂ O); (Found: C, 54.39; H, 5.30; N, 11.87. C₁₇ H₂₀ N₄.2 (C₂ H₂O₄)0.2H₂ O requires C, 54.36; H, 5.30; N, 12.07%); ¹ H NMR (360 MHz, D₂O) δ2.26-2.45 (1H, m, CH of CH₂); 2.55 (3H, s, Me); 2.62-2.75 (1H, m, CHof CH₂); 3.02 and 3.03 (total 3H, s, Me); 3.23-3.45 (2H, m, CH₂);3.60-3.68, 3.77-4.1 and 4.12-4.15 (total 3H, each m, CH and CH₂); 7.30(1H, d, J=8.9 Hz, Ar--H); 7.48 (1H, d, J=2.2 Hz, Ar--H); 7.52 (1H, s,Ar--H); 7.53 (1H, d, J=2.2 Hz, Ar--H); 7.70 (1H, d, J=8.9 Hz, Ar--H);7.78 (1H, s, Ar--H).

EXAMPLE 28 1H-4-[5-Imidazol-1-yl-1H-indol-3-yl]piperidine. Bisoxalate

Prepared from N-benzyl-4-(formylmethyl)piperidine and4-(imidazolyl)phenyl hydrazine hydrochloride using the proceduresdescribed for Examples 22 and 24. The bisoxalate salt was prepared, mp155°-157° C.; (Found: C, 54.32; H, 5.50; N, 11.66. C₁₆ H₁₈ N₄.2(C₂ H₂O₄).0.3(Et₂ O) requires C, 54.33; H, 5.38; N, 11.96%); ¹ H NMR (360 MHz,D₂ O) δ1.90-2.04 (2H, m, CH₂); 2.32 (2H, br d, J=13 Hz, CH₂); 3.20-3.32(3H, m, CH and CH₂); 3.55-3.60 (2H, m, CH₂); 7.41-7.44 (2H, m, Ar--H);7.64 (1H, s, Ar--H); 7.68 (1H, d, J=8.7 Hz, Ar--H); 7.85 (1H, s, Ar--H);7.92 (1H, d, J=2 Hz, Ar--H); 9.06 (1H, s, Ar--H).

EXAMPLE 29 1H-4-[5-(1,2,3-Triazol-1-yl)-1H-indol-3-yl]piperidine.Hemioxalate

Prepared from N-benzyl-4-(formylmethyl)piperidine and4-(1,2,3-triazolyl)phenyl hydrazine hydrochloride using the proceduresdescribed for Examples 22 and 24. The hemioxalate salt was prepared, mp278° C. (MeOH/Et₂ O); (Found: C, 61.84; H, 6.10; N, 22.21. C₁₅ H₁₇N₅.0.5(C₂ H₂ O₄ requires C, 61.53; H, 5.81; N, 22.42%); ¹ H NMR (360MHz, D₆ -DMSO) δ1.66-1.82 (2H, m, CH₂); 1.98-2.06 (2H, m, CH₂);2.83-2.89 (2H, m, CH₂); 2.98-3.08 (1H, m, CH); 3.21 (2H, br d, J=12.5Hz, CH₂); 7.28 (1H, s, Ar--H); 7.51-7.56 (2H, m, Ar--H); 7.93 (1H, s,Ar--H); 8.05 (1H, s, Ar--H); 8.73 (1H, s, Ar--H).

EXAMPLE 30 N-Methyl-4-[5-imidazol-1-yl-1H-indol-3-yl]piperidine.Sesquioxalate

Prepared from N-methyl-4-(formylmethyl)piperidine and4-(imidazolyl)phenyl hydrazine hydrochloride as described for Example22. The sesquioxalate salt was prepared, mp 217° C.; (Found: C, 57.41;H, 5.83; N, 13.30. C₁₇ H₂₀ N₄. 1.5(C₂ H₂ O₄).0.14(CH₃ OH) requires C,57.61; H, 5.66; N, 13.34%); ¹ H NMR (360 MHz, D₂ O) δ1.94-2.06 (2H, m,CH₂); 2.34-2.38 (2H, m, CH₂); 2.94 (3H, s, CH₃); 3.20-3.27 (3H, m, CHand CH₂); 3.63-3.67 (2H, m, CH₂); 7.40-7.43 (2H, m, Ar--H); 7.64 (1H, s,Ar--H); 7.68 (1H, d, J=8.7 Hz, Ar--H); 7.84 (1H, s, Ar--H); 7.90 (1H, d,J=1.3 Hz, Ar--H); 9.07 (1H, s, Ar--H).

EXAMPLE 31 N-Methyl-4-[5-(1,2,3-triazol-1-yl )-1H-indol-3-yl]piperidine.Hemioxalate

Prepared from N-methyl-4-(formylmethyl)piperidine and4-(1,2,3-triazolyl)phenyl hydrazine hydrochloride as described forExample 22. The hemioxalate salt was prepared, mp 251°-254° C. (MeOH/Et₂O); (Found: C, 62.21; H, 6.49; N, 21.21. C₁₆ H₁₉ N₅.0.5(C₂ H₂ O₄).0.1H₂O requires C, 62.22; H, 6.20; N, 21.34%); ¹ H NMR (360 MHz, D₂ O)δ1.69-2.01 (2H, m, CH₂); 2.25-2.31 (2H, m, CH₂); 2.94 (3H, s, CH₃);3.04-3.20 (3H, m, CH and CH₂); 3.61-3.65 (2H, m, CH₂); 7.32 (1H, s,Ar--H); 7.44 (1H, dd, J=1.9 and 8.7 Hz, Ar--H); 7.58 (1H, d, J=8.7 Hz,Ar--H); 7.86 (1H, d, J=1.8 Hz, Ar--H); 7.94 (1H, s, Ar--H); 8.29 (1H, s,Ar--H).

EXAMPLE 32 N-Methyl-3-[5-(1,2,3-triazol-1-yl)-1H-indol-3-yl]pyrrolidine. Oxalate

Prepared from N-benzyl-3-(formylmethyl)pyrrolidine and4-(1,2,3-triazolyl)phenyl hydrazine hydrochloride as described forExamples 26 and 27. The oxalate salt was prepared, mp 154°-156° C.(MeOH/Et₂ O); (Found: C, 57.06; H, 5.39; N, 19.43. C₁₅ H₁₇ N₅.C₂ H₂ O₄requires C, 57.14; H, 5.36; N, 19.60%); ¹ H NMR (360 MHz, D₂ O)δ2.23-2.38 (1H, m, CH of CH₂); 2.55-2.69 (1H, m, CH of CH₂); 3.01 (3H,s, Me); 3.13-3.42 and 3.55-3.60 (total 2H, each m, CH₂); 3.70-4.09 (3H,m, CH and CH₂); 7.39 (1H, d, J=8.7 Hz, Ar--H); 7.42-7.46 (1H, m, Ar--H);7.58 (1H, d, J=8.7 Hz, Ar--H); 7.62 (1H, s, Ar--H); 7.93 (1H, s, Ar--H);8.30 (1H, s, Ar--H).

EXAMPLE 33N-Methyl-3-[5-(2-methylimidazol-1-ylmethyl)-1H-indol-3-yl]pyrrolindine.Bisoxalate

Prepared from N-benzyl-3-(formylmethyl)pyrrolidine and4-(2-(methyl)imidazol-1-ylmethyl)phenyl hydrazine hydrochloride asdescribed for Examples 26 and 27. The bisoxalate salt was prepared, mp152°-153° C.; (Found: C, 55.41; H, 5.51; N, 11.61. C₁₈ H₂₂ N₄.2 (C₂H₂₀₄) requires C, 55.69; H, 5.52; N, 11.81%); ¹ H NMR (360 MHz, D₂ O)δ2.22-2.46 (1H, m, CH of CH₂); 2.58-2.76 (1H, m, CH of CH₂); 2.65 (3H,s, Me); 3.02 and 3.03 (total 3H, s, Me); 3.21-3.44, 3.60-3.67, 3.75-3.95and 4.09-4.14 (total 5H, each m, CH and 2 of CH₂); 5.42 (2H, s, CH₂);7.17-7.19 (1H, m, Ar--H); 7.32 (2H, s, Ar--H); 7.39 (1H, d, J=8.4 Hz,Ar--H); 7.56 (1H, d, J=8.4 Hz, Ar--H); 7.67 (1H, s, Ar--H).

EXAMPLE 34 N-Methyl-3-[5-imidazol-1-yl-1H-indol-3-yl]pyrrolidine.Bisoxalate

Prepared from N-benzyl-3-(formylmethyl)pyrrolidine and4-(imidazolyl)phenyl hydrazine hydrochloride using the proceduresdescribed for Examples 26 and 27. The bisoxalate salt was prepared, mp173°-175° C. (MeOH/Et₂ O); (Found: C, 53.94; H, 5.07; N, 12.51.C₁₆ H₁₈N₄.2 (C₂ H₂ O₄) requires C, 53.81; H, 4.97; N, 12.55%); ¹ H NMR (360MHz, D₂ O) δ2.26-2.45 and 2.60-2.78 (each 1H, each m, CH₂), 3.02 and3.03 (total 3H, each s, Me), 3.23-3.45, 3.61-3.66, 3.78-3.95 and4.11-4.16 (total 5H, each m, 2 of CH₂ and CH), 7.42 and 7.45 (total 1H,each s, Ar--H), 7.49 (1H, d, J=9.2 Hz, Ar--H), 7.65 (1H, s, Ar--H), 7.69(1H, d, J=9.2 Hz, Ar--H), 7.86-7.89 (2H, m, Ar--H), 9.09 (1H, s, Ar--H).

EXAMPLE 35N-Methyl-3-[5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl]pyrrolidine.Sesquioxalate. Hemihydrate

Prepared from N-benzyl-3-(formylmethyl)pyrrolidine and4-(1,2,4-triazolylmethyl)phenyl hydrazine dihydrochloride as describedfor Examples 26 and 27. The sesquioxalate hemihydrate salt was prepared,mp 59°-61° C. (isopropyl alcohol/Et₂ O); (Found: C, 55.10; H, 5.79; N,16.99. C₁₆ H₁₉ N₅.1.3(C₂ H₂ O₄).0.4H₂ O requires C, 55.08; H, 5.57; N,17.27%); ¹ H NMR (360 MHz, D₂ O) δ2.20-2.42 and 2.54-2.72 (each 1H, eachm, CH₂), 3.00 and 3.02 (total 3H, each s, Me), 3.16-3.42, 3.56-3.62,3.72-3.76, 3.82-3.94 and 3.98-4.10 (total 5H, each m, 2 of CH₂ and CH),5.52 (2H, s, CH₂), 7.22 and 7.24 (total 1H, each s, Ar--H), 7.34 (1H, d,J=8.6 Hz, Ar--H), 7.52 (1H, d, J=8.6 Hz, Ar--H), 7.66 (1H, s, Ar--H),8.06 (1H, s, Ar--H), 8.58 (1H, s, Ar--H).

EXAMPLE 36 N-Methyl-3-[5-imidazol-1-ylmethyl-1H-indol-3yl]pyrrolidine.Oxalate. Hemihydrate

Prepared from N-benzyl-3-(formylmethyl)pyrrolidine and4-(imidazol-1-ylmethyl)phenyl hydrazine hydrochloride as described forExamples 26 and 27. The oxalate hemihydrate salt was prepared, mp101°-104° C. (isopropyl alcohol/Et₂ O); (Found: C, 59.51; H, 6.35; N,14.54. C₁₇ H₂₀ N₄.C₂ H₂ O₄.0.6H₂ O. 0.1 (^(i) PrOH) requires C, 59.86;H, 6.25; N, 14.47%); ¹ H NMR (360 MHz, D₂ O) δ2.26-2.42 (1H, m, CH ofCH₂), 2.60-2.74 (1H, m, CH of CH₂), 3.03 (3H, s, Me), 3.16-4.12 (5H, brm, 2 of CH₂ and CH), 5.45 (3H, s, Me), 7.27 (1H, dd, J=1.6 and 8.5 Hz,Ar--H), 7.31 (1H, s, Ar--H), 7.38-7.40 (2H, m, Ar--H), 7.58 (1H, d,J=8.5 Hz, Ar--H), 7.70 (1H, s, Ar--H), 8.39 (1H, s, Ar--H).

EXAMPLE 37N,N-Dimethyl-2-[5-(2-aminoimidazol-1-yl)-1H-indol-3-yl]ethylamine.Bisoxalate

Prepared from 2-aminoimidazole and 4-fluoro nitrobenzene as describedfor Example 16. To prevent reaction of the aminoimidazole with sodiumnitrite under the diazotization conditions the amino was protected asthe acetamide with Ac₂ O/AcOH prior to hydrogenation and hydrazineformation. Fischer reaction of 4-[2-(methylcarbonylamino)imidazol-1-yl]phenyl hydrazine with N,N-dimethylaminobutanaldimethylacetal gave the title-product. The bisoxalate salt was prepared,mp 199°-200° C. (MeOH/Et₂ O); (Found: C, 50.35; H, 5.06; N, 15.05. C₁₅H₁₉ N₅.2.1(C₂ H₂ O₄) requires C, 50.31; H, 5.10; N, 15.28%); ¹ H NMR(360 MHz, D₂ O) δ2.91 (6H, s, N(Me)₂), 3.27 (2H, t, J=7.4 Hz, CH₂), 3.50(2H, t, J=7.4 Hz, CH₂), 6.97 (2H, s, Ar--H), 7.29 (1H, dd, J=1.8 and 8.7Hz, Ar--H), 7.48 (1H, s, Ar--H), 7.67 (1H, d, J=8.7 Hz, Ar--H), 7.78(1H, d, J=1.8 Hz, Ar--H).

EXAMPLE 38N,N-Dimethyl-2-[5-(2-aminoimidazol-1-ylmethyl)-1H-indol-3-yl]ethylamine.Sesquioxalate

1.4-Cyanophenylhydrazine Hydrochloride

To a cooled (-15° C.) and stirred suspension of 4-aminobenzonitrile (50g, 423 mmol) in concentrated hydrochloric acid (550 ml) was addeddropwise a solution of sodium nitrite (31.5 g, 457 mmol) in water (200ml) at such a rate as to maintain the temperature below -10° C. Afterthe addition was finished, the reaction mixture was quickly filtered toremove solids and the filtrate was added portionwise to a cooled (-20°C.) and stirred solution of tin (II) chloride dihydrate (477 g, 2.1 mol)in concentrated hydrochloric acid (370 ml) at such a rate as to maintainthe temperature below -10° C. After further 15 minutes at -10° to 0° C.,the white precipitate was collected by filtration, washed with diethylether (4×250 ml) and dried to give 56 g (78%) of the title compound; mp235°-237° C. (ethanol-water 1:1); ¹ H NMR (250 MHz, DMSO-d₆) δ10.50 (3H,br s, --N⁺ H₃), 9.10 (1H, br s, --NH--), 7.71 (2H, d, J=8.8 Hz, Ar--H),7.03 (2H, d, J=8.8 Hz, Ar--H); m/z (CI) 132 (M⁺ -1).

2. 2-[5-Cyano-1H-indol-3-yl]ethylamine. Hydrochloride

To a stirred suspension of 4-cyanophenylhydrazine (50 g) in a mixture ofethanol and water (5:1; 21) was added 4-chlorobutanal dimethylacetal (45g) and the resulting mixture was refluxed for 18 hours. Solvents wereremoved under vacuum and the residue was azeotroped with toluene to givea brown solid. Crystallisation of this crude material from methanol (150ml) gave 23 g (35%) of the title compound as a yellow solid; mp270°-274° C.; ¹ H NMR (250 MHz, DMSO-d₆) δ11.60 (1H, br s, indole N--H),8.17 (1H, d, J=1.1 Hz, Ar--H), 7.97 (3H, br s, --N⁺ H₃), 7.54 (1H, d,J=8.5 Hz, Ar--H), 7.46 (1H, s, Ar--H), 7.44 (1H, dd, J=8.5 and 1.1 Hz,Ar--H), 3.05 (4H, br s, --CH₂ CH₂ N--); m/z (CI) 184 (M⁺ -1).

3. N-tert-Butyloxycarbonyl,2-[5-cyano-1H-indol-3yl]ethylamine.

The title compound was prepared in 58% yield from the precedingtryptamine using the conditions described for Example 1 (Step 4); whitesolid; mp 132°-134° C. (hexane-ethyl acetate); ¹ H NMR (250 MHz, CDCl₃)δ8.42 (1H, br s, indole NH), 7.93 (1H, s, Ar--H), 7.41 (2H, s, Ar--H),7.12 (1H, d, J=2.2 Hz, Ar--H), 4.71 (1H, br s, -NH-), 3.44 (2H, q, J=6.9Hz, --CH₂ NH--), 2.94 (2H, t, J=6.9 Hz, Ar--CH₂₋), 1.45 (9H, s, t-Bu);m/z (CI) 286 (M⁺ +1).

4. N-tert-Butyloxycarbonyl-2-[5-aminomethyl-1H-indol-3yl]ethylamine.

A solution of the product from the previous step (11.3 g) in a mixtureof absolute ethanol (750 ml) and chloroform (22 ml) was hydrogenated at50 psi over platinum (IV) oxide (1 g) for 28 hours. The catalyst wasremoved by filtration and solvents were o removed under vacuum. Flashchromatography of the residue (silica gel,dichloromethane-methanol-ammonia 90:10:1)gave 9.5 g (82%) of the titlecompound as a white solid; mp 147°-149° C.; ¹ H NMR (360 MHz, CDCl₃)δ8.04 (1H, br s, indole N--H), 7.52 (1H, s, Ar--H), 7.33 (1H, d, J=8.4Hz, Ar--H), 7.16 (1H, d, J=8.4 Hz, Ar--H), 7.03 (1H, s, Ar--H), 4.61(1H, br s, --NHBOC), 3.96 (2H, s, Ar--CH₂ NH₂), 3.45 (2H, br q, --CH₂NBOC), 2.95 (2H, t, J=6.8 Hz, Ar--CH₂ --), 1.43 (9H, s, t--Bu); m/z (CI)288 (M⁺ -1).

5.N-tert-Butyloxycarbonyl-2-[5-dimethylaminomethyl-1H-indol-3-yl]ethylamine.

The title compound was prepared in 71% yield from the product from theprevious step using the conditions described for Example 3 (Step 3);colourless thick oil; ¹ H NMR (250 MHz, CDCl₃) δ8.07 (1H, br s, indoleN--H), 7.50 (1H, s, Ar--H), 7.31 (1H, d, J=8.3 Hz, Ar--H), 7.16 (1H, d,J=8.3 Hz, Ar--H), 7.02 (1H, s, Ar--H), 4.61 (1H, br s, --NH--), 3.54(2H, s, Ar--CH₂ N-), 3.45 (2H, q, J=6.2 Hz, --CH₂ NH--), 2.94 (2H, t,J=6.2 Hz, Ar--CH₂₋), 2.27 (6H, s, --NMe₂), 1.43 (9H, s, t--Bu).

6. N-tert-Butyloxycarbonyl-2-[5-trimethylammoniummethyl-1H-indol-3-yl]ethylamine. Iodide

A solution of the product from step 5 (2.9 g) in a mixture of anhydrousdiethyl ether (170 ml) and iodomethane (36 ml) was allowed to stand atroom temperature for 16 hours in the dark. The white solid was collectedby filtration, washed with diethyl ether and dried over phosphorouspentoxide at 50° C. under vacuum to give 4.2 g (100%) of the titlecompound; mp 199°-202° C. (decomposition); ¹ H NMR (360 MHz, DMSO-d₆)δ11.09 (1H, br s, indole N--H), 7.69 (1H, s, Ar--H), 7.44 (1H, d, J=8.3Hz, Ar--H), 7.26 (1H, s, Ar--H), 7.19 (1H, d, J=8.3 Hz, Ar--H), 6.89(1H, br t, --NH--), 4.57 (2H, s, Ar--CH₂ N--), 3.23 (2H, q, J=7.6 Hz,--CH₂ NH--), 3.01 (9H, s, --N⁺ Me₃), 2.83 (2H, t, J=7.6 Hz, Ar--CH₂ --),1.37 (9H, s, t--Bu); m/z (FAB) 332. (Found: C, 49.30; H, 6.55; N, 8.79.C₁₉ H₃₀ IN₃ O₂ requires: C, 49.68; H, 6.58; N, 9.15%).

7.N-tert-Butyloxycarbonyl-2-[5-(2-nitroimidazol-1-ylmethyl)-1H-indol-3-yl]ethylamine.

Sodium hydride (0.6 g of a 60% dispersion in oil) was added to a stirredsolution of 2-nitroimidazole (1.61 g, 14.2 mmol) in DMF (65 ml), at roomtemperature. After 0.5 h, a solution of the preceding methiodide (3.26g, 7.1 mmol) in DMF (40 ml) was added and the mixture refluxed for 2 hand then stirred at room temperature for 18 h. Aqueous work-up followedby flash chromatography of the crude product, afforded thetitle-compound (2.6 g); ¹ H NMR (360 MHz, CDCl₃) δ1.43 (9H, s, t-Bu),2.94 (2H, t, J=7.0 Hz, CH₂), 3.40-3.48 (2H, m, CH₂), 5.69 (2H, s, CH₂),7.01 (1H, s, Ar--H), 7.09 (1H, d, J=8.4 Hz, Ar--H), 7.10 (2H, s, Ar--H),7.37 (1H, d, J=8.4 Hz, Ar--H), 7.54 (1H, s, Ar--H), 8.12 (1H, s,indole-NH).

8.2-[5-(2-Nitroimidazol-1-ylmethyl)-1H-indol-3-yl]ethylamine.

A solution of the preceding imidazole (2.6 g, 6.7 mmol) in 90% HCO₂ H)(150 ml) was stirred at room temperature for 1.25 h. The reaction wasquenched by addition of MeOH and the solvents removed under vacuum. Thecrude product was purified by flash chromatography on silica-gel elutingwith CH₂ Cl₂ /EtOH/NH₃ (30:8:1). The product (0.73 g) was obtained as ayellow oil; ¹ H NMR (360 MHz, d₄ -MeOH) δ2.87-2.94 (4H, m, 2 of CH₂),5.71 (2H, s, CH₂), 7.05 (1H, d, J=8.4 Hz, Ar--H), 7.11 (1H, s, Ar--H),7.12 (1H, s, Ar--H), 7.35 (1H, d, J=8.4 Hz, Ar--H), 7.39 (1H, s, Ar--H),7.55 (1H, s, Ar--H).

9.N,N-Dimethyl-2-[5-(2-nitroimidazol-1-ylmethyl)-1H-indol-3-yl]ethylamine.

Prepared from the preceding tryptamine using the conditions describedfor Example 3(Step 3); ¹ H NMR (250 MHz, CDCl₃) δ2.33 (6H, s, N(Me)2),2.62 (2H, t, J=7.4 Hz, CH₂), 2.92 (2H, t, J=7.4 Hz, CH₂), 5.68 (2H, s,CH₂), 7.00 (1H, d, J=1.0 Hz, Ar--H), 7.07 (1H, dd, J=1.0 and 8.2 Hz,Ar--H), 7.09 (1H, d, J=2.4 Hz, Ar--H), 7.10 (1H, d, J=2.4 Hz, Ar--H),7.35 (1H, d, J=8.2 Hz, Ar--H), 7.53 (1H, s, Ar--H), 8.19 (1H, br s,indole-NH).

10.N,N-Dimethyl-2-[5-(2-aminoimidazol-1-ylmethyl)-1H-indol-3-yl]ethylamine.Sesquioxalate

The title-compound was prepared from the product of Step 9 using theconditions described for Example 5 (Step 2). The sesquioxalate salt wasprepared, mp 211°-212° C. (MeOH/Et₂ O); (Found: C, 54.46; H, 6.08; N,16.53. C₁₆ H₂₁ N₅.1.5(C₂ H₂ O₄).0.06 (MeOH) requires C, 54.46; H, 5.81;N, 16.66%); ¹ H NMR (360 MHz, D₂ O) δ2.91 (6H, s, N(Me)₂), 3.25 (2H, t,J=7.4 Hz, CH₂), 3.49 (2H, t, J=7.4 Hz, CH₂), 5.16 (2H, s, CH₂), 6.77(1H, d, J: 2.3 Hz, Ar--H), 6.83 (1H, d, J=2.3 Hz, Ar--H), 7.19 (1H, dd,J=1.5 and 8.5 Hz, Ar--H), 7.39 (1H, s, Ar--H), 7.56 (1H, d, J=8.5 Hz,Ar--H), 7.61 (1H, s, Ar--H).

EXAMPLE 39N-Methyl-2-[5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl]ethylamine.Oxalate.

1. N-Benzyl-2-[5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl]ethylamine.

To a solution of 2-[5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3yl]ethylamine(1.5 g, 6.2 mmol) in EtOH (30ml) was added freshly distilledbenzaldehyde (0.66 g, 6.2 mmol) and the solution stirred at roomtemperature for 21 h. NaBH₄ (0.24 g, 6.3 mmol) was added portionwiseover 10 min, at room temperature, and the resulting mixture was stirredfor 0.5 h before the solvent was removed under vacuum. The resultingresidue was taken up into water (10 ml) and acidified with 1N HCl (15ml). The mixture was then basified with 2N NaOH and extracted with EtOAc(4×50 ml). The combined organic phases were washed with brine (30 ml),dried and concentrated. Chromatography of the residue on silica-geleluting with CH₂ Cl₂ /MeOH (85:15) gave the title-product (1.38 g, 67%);¹ H NMR (360 MHz, CDCl₃) δ2.94 (4H, s, 2 of CH₂), 3.80 (2H, s, CH₂),5.38 (2H, s, CH₂), 7.04 (1H, d, J=2 Hz, Ar--H), 7.08 (1H, dd, J=1.5 and8.4 Hz, Ar--H), 7.18-7.30 (5H, m, Ar--H) 7.32 (1H, d, J=8.4 Hz, Ar--H),7.54 (1H, s, Ar--H), 7.94 (1H, d, J=2 Hz, Ar--H), 8.17 (1H, br s,indole-NH).

2.N-Benzyl-N-methyl-2-[5-(1,2.4-triazol-1-ylmethyl)-1H-indol-3-yl]ethylamine.

To a stirred solution of the preceding amine (1.14 g, 3.4 mmol) inanhydrous DMF (45 ml) was added K₂ CO₃ (0.89 g, 6.4 mmol) and dimethylsulphate (0.46 g, 3.7 mmol). The mixture was stirred at room temperaturefor 3.5 h before adding H₂ O (90 ml) and extracting with EtOAc (2×100ml). The combined organic solutions were washed with brine (40 ml),dried, and concentrated. The residue was chromatographed on silica-geleluting with CH₂ Cl₂ /MeOH (90:10) to give the desired product (0.69 g);¹ H NMR (360 MHz, CDCl₃) δ2.34 (3H, s, CH₃), 2.70-2.76 (2H, m, CH₂),2.94-3.00 (2H, m, CH₂), 3.60 (2H, s, CH₂), 5.38 (2H, s, CH₂), 7.04 (1H,d, J=2 Hz, Ar--H), 7.08 (1H, dd, J=2 and 8.4 Hz, Ar--H), 7.20-7.36 (6H,m, Ar--H), 7.44 (1H, s, Ar--H), 7.94 (1H, s, Ar--H), 7.96 (1H, s,Ar--H), 8.18 (1H, br s, indole-NH).

3. N-Methyl-2,-[5-(1,2,4,triazol-1-ylmethyl )-1H-indol-3-yl]ethylamine.Oxalate.

A solution of the preceding benzylamine (0.69 g, 2.0 mmol) in ethanol(100 ml) and 2N HCl (2 ml) was hydrogenated at 30 psi over 10% Pd/C (0.6g) for 4 h. The catalyst was removed by filtration through hyflo, thesolvent removed under vacuum, and the residue chromatographed onsilica-gel eluting with CH₂ C₁₂ /EtOH/NH₃ (40:8:1) to give thetitle-N-methylamine (0.34 g, 68%). The oxalate salt was prepared andrecrystallised from isopropyl alcohol; mp 149°-150° C.; (Found: C,55.42; H, 5.72; N, 19.55. C₁₄ H₁₇ N₅.C₂ H₂ O₄.0.15 (iPA) requires C,55.72; H, 5.75; N, 19.76%); ¹ H NMR (360 MHz, D₂ O) δ2.44 (3H, s, CH₃),2.87-2.98 (4H, m, 2 of CH₂), 5.41 (2H, s, CH₂), 7.05 (1H, s, Ar--H),7.09 (1H, dd, J=1.6 and 8.4 Hz, Ar--H), 7.31 (1H, d, J=8.4 Hz, Ar--H),7.57 (1H, s, Ar--H), 7.96 (1H, s, Ar--H), 7.99 (1H, s,

EXAMPLE 40 Tablet Preparation

Tablets containing 1.0, 2.0, 25.0, 26.0, 50.0 and 100.0 mg, respectivelyof the following compounds are prepared as illustrated below:

N,N-Dimethyl-2-[5-(2-methyltetrazol-5-ylmethyl)-1H-indol-3-yl]ethylamine.Oxalate.

N,N-Dimethyl-2-[5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl]ethylamine.Benzoate.

N,N-Dimethyl-2-[5-(1,2,3,4-tetrazol-1-ylmethyl)-1H-indol-3-yl]ethylamine.Succinate.

N-Methyl-4-[5-imidazol-1-yl-1H-indol-3-yl]piperidine. Sesquioxalate.

N-Methyl-3-[5-(1,2,3-triazol-1-yl)-1H-indol-3-yl]pyrrolidine. Oxalate.

    ______________________________________                                        TABLE FOR DOSES CONTAINING FROM                                               1-25 MG OF THE ACTIVE COMPOUND                                                               Amount-mg                                                      ______________________________________                                        Active Compound  1.0        2.0    25.0                                       Microcrystalline cellulose                                                                     49.25      48.75  37.25                                      Modified food corn starch                                                                      49.25      48.75  37.25                                      Magnesium stearate                                                                             0.50       0.50   0.50                                       ______________________________________                                    

    ______________________________________                                        TABLE FOR DOSES CONTAINING FROM                                               26-100 MG OF THE ACTIVE COMPOUND                                                             Amount-mg                                                      ______________________________________                                        Active Compound  26.0       50.0   100.0                                      Microcrystalline cellulose                                                                     52.0       100.0  200.0                                      Modified food corn starch                                                                      2.21       4.25   8.5                                        Magnesium stearate                                                                             0.39       0.75   1.5                                        ______________________________________                                    

All of the active compound, cellulose, and a portion of the corn starchare mixed and granulated to 10% corn starch paste. The resultinggranulation is sieved, dried and blended with the remainder of the cornstarch and the magnesium stearate. The resulting granulation is thencompressed into tablets containing 1.0 mg, 2.0 mg, 25.0 mg, 26.0 mg,50.0 mg and 100 mg of the active ingredient per tablet.

What claimed is:
 1. A compound of formula I, or a pharmaceuticallyacceptable salt thereof: ##STR36## wherein the broken circle representstwo non-adjacent double bonds in any position in the five-memberedring;two, three or four of V, W, X, Y and Z represent nitrogen and theremainder represent carbon provided that, when two of V, W, X, Y and Zrepresent nitrogen and the remainder represent carbon, then the saidnitrogen atoms are in non-adjacent positions within the five-memberedring; A¹ represents hydrogen, methyl, ethyl, benzyl or amino; A²represents a non-bonded electron pair when four of V, W, X, Y and Zrepresent nitrogen and the other represents carbon; or, when two orthree of V, W, X, Y and Z represent nitrogen and the remainder representcarbon, A² represents hydrogen, methyl, ethyl, benzyl or amino; Erepresents a bond or a straight or branched alkylene chain containingfrom 1 to 4 carbon atoms; F represents a group of formula ##STR37## Urepresents or C--R² ; B represents N--R³ ; R¹ represents --CH₂ •CHR⁴•NR⁶ R⁷ ; and R², R³, R⁴, R⁶ and R⁷ independently represent hydrogen orC₁₋₆ alkyl; with the exception of the compoundN,N-dimethyl-2-[5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl]ethylamineand pharmaceutically acceptable salts thereof.
 2. A compound as claimedin claim 1 represented by formula IIA, and pharmaceutically acceptablesalts thereof: ##STR38## wherein X¹ represents nitrogen or A¹² --C;n iszero, 1, 2 or 3; B¹ represents N--R¹³ ; A¹¹ and A¹² independentlyrepresent hydrogen, methyl, ethyl, benzyl or amino; and R¹², R¹³, R¹⁴,R¹⁶ and R¹⁷ independently represent hydrogen or C₁₋₆ alkyl.
 3. Acompound as claimed in claim 1 represented by formula lIB, andpharmaceutically acceptable salts thereof: ##STR39## wherein Y¹represents nitrogen or A²² --C;n is zero, 1, 2 or 3; B² representsN--R²³ ; A²¹ and A²² independently represent hydrogen, methyl, ethyl orbenzyl; and R²², R²³, R²⁴, R²⁶ and R²⁷ independently represent hydrogenor C₁₋₆ alkyl.
 4. A compound as claimed in claim 1 represented byformula IIC, and pharmaceutically acceptable salts thereof: ##STR40##wherein Y² represents nitrogen or A³² --C;Z¹ represents nitrogen or CH;n is zero, 1, 2 or 3; B³ represents N--R³³ ; A³¹ and A³² independentlyrepresent hydrogen, methyl or amino; R³¹ represents --CH₂ •CHR³⁴ •NR³⁶R³⁷ ; and R³², R³³, R³⁴, R³⁶ and R³⁷ independently represent hydrogen orC₁₋₆ alkyl;with the exception of the compoundN,N-dimethyl-2-[5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl]ethylamineand pharmaceutically acceptable salts thereof.
 5. A compound as claimedin claim 1 represented by formula IID, and pharmaceutically acceptablesalts thereof: ##STR41## wherein W¹ represents nitrogen or C--A^(42;) nis zero, 1, 2 or 3; B⁴ represents N-R⁴³ ; A⁴¹ and A⁴² independentlyrepresent hydrogen or methyl; R⁴¹ represents --CH₂ •CHR⁴⁴ •NR⁴⁶ R⁴⁷ ;and R⁴², R⁴³, R⁴⁴, R⁴⁶ and R⁴⁷ independently represent hydrogen or C₁₋₆alkyl.
 6. A compound as claimed in claim 1 selectedfrom:2-[5-(2-benzyltetrazol-5-ylmethyl)-1H-indol-3-yl]ethylamine;2-[5-(1-benzyltetrazol-5-ylmethyl)-1H-indol-3-yl]ethylamine;N,N-dimethyl-2-[5-(1-methyltetrazol-5-ylmethyl)-1H-indol-3-yl]ethylamine;N,N-dimethyl-2-[5-(2-methyltetrazol-5-ylmethyl)-1H-indo-3-yl]ethylamine;N,N-dimethyl-2-[5-(tetrazol-2-ylmethyl)-1H-indol-3-yl]ethylamine;N,N-dimethyl-2-[5-(tetrazol-1-ylmethyl)-1H-indol-3-yl]ethylamine;N,N-dimethyl-2-[5-(1-methyl-1,2,4-triazol-5-ylmethyl)-1H-indol-3-yl]ethylamine;N,N-dimethyl-2-[5-(1-methyl-1,2,4-triazol-3-ylmethyl)-1H-indol-3-yl]ethylamine;N,N-dimethyl-2-[5-(1,2,3-triazol-1-ylmethyl)-1H-indol-3-yl]ethylamine;N,N-dimethyl-2-[5-(2-methylimidazol-1-ylmethyl)-1H-indo 1-3-yl]ethylamine;N,N-dimethyl-2-[5-(imidazol-1-ylmethyl)-1H-indol-3-yl]ethylamine;N,N-dimethyl-2-[5-(2-methylimidazol-1-yl)-1H-indol-3-yl]ethylamine;N,N-dimethyl-2-[5-(2-ethyltetrazol-5-ylmethyl)-1H-indol-3-yl]ethylamine;N,N-dimethyl-2-[5-(1-ethyltetrazol-5-ylmethyl)-1H-indo -3-yl]ethylamine;N,N-dimethyl-2-[5-(1,2,4-triazol-1-yl)-1H-indol-3-yl]ethylamine;N,N-dimethyl-2-[5-(2-aminoimidazol-1-yl)-1H-indol-3-yl]ethylamine;N,N-dimethyl-2-[5-(2-aminoimidazol-1-ylmethyl)-1H-indol-3-yl]ethylamine;N-methyl-2-[5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl]ethylamine;andpharmaceutically acceptable salts thereof.
 7. A pharmaceuticalcomposition comprising an effective amount of a compound as claimed inclaim 1 in association with a pharmaceutically acceptable carrier orexcipient.
 8. A method for the treatment and/or prevention of migraineand associated conditions, which method comprises administering to apatient in need of such treatment an effective amount of a compound offormula I according to claim 1 or a pharmaceutically acceptable saltthereof.